Device sorts microscopic particles
with speed and precision
a remarkable collaboration between engineers, physicists
and biologists, Princeton scientists have invented a
device that rapidly sorts microscopic particles into
extremely fine gradations of sizes, opening a range
of potential uses.
The researchers have used the device to sort particles
ranging in size from bacterial cells to large segments
of DNA and reported their results in the May 14 issue
of Science. The technology could greatly accelerate
the work of sequencing genomes and could find uses in
many other areas, from improving the performance of
pharmaceuticals to detecting bioterrorism agents.
Until now there was no way to sort large quantities
of molecules or cells by size with such speed and precision,
according to the researchers. Current methods separate
particles only according to major differences in size
and, for particles such as DNA, can take hours to perform.
The Princeton invention can distinguish large quantities
of particles that are 1.00 micrometer (a millionth of
a meter) from others that are 1.005 microns in a matter
The device is dubbed a "tango array" for the
precise choreography it imposes upon particles.
The discovery was led by Lotien R. Huang, a postdoctoral
researcher in electrical engineering, and grew out of
a long-term collaboration between James Sturm, professor
of electrical engineering, Robert Austin, a professor
of physics, and Edward Cox, a professor of molecular
biology, all of whom are co-authors of the Science paper.
The group, which is part of the newly formed Princeton
Institute for the Science and Technology of Materials,
has produced a variety of devices for sorting DNA and
other particles, but none as fast and precise as the
The trade-off between speed and precision had seemed
insurmountable, said Huang, who has been building and
testing sorting devices for nearly six years. The breakthrough
came when a collaborator in the physics department,
former postdoctoral researcher Jonas Tegenfeldt, challenged
Huang to come up with a mathematical description of
how his earlier attempts at sorting devices worked:
If he altered a device, could he predict exactly how
its performance would change?
"At first I thought such an analytical model would
be impossible because the structures were so complicated,
but Jonas got me thinking," said Huang, who has
been working on the problem for six years. Within a
few days, Huang not only derived a mathematical theory,
but had an insight into making an entirely new device
that has virtually no trade-off between speed and accuracy.
Huang quickly made a prototype device and tested it
with tiny plastic beads. "It gives such amazing
separation resolution in just a minute," he said.
"And the operation is very simple: You just need
a syringe to push your sample through. We are very excited
The device consists of an array of microscopic pillars
etched into silicon. Air from a syringe or other pump
forces a liquid suspension of particles through the
pillar array, which guides the particles into different
paths. When the particles emerge from the array, they
have been sorted into any number of "channels"
according to size. A device less than 1 square inch
could easily yield hundreds of channels, each just 1
percent different in size.
The device works in a unique way because the arrangement
of pillars forces particles along completely predetermined
paths, like pennies and dimes rolling through a child's
coin sorter. Previous attempts required the particles
to diffuse randomly so that bigger particles slowly
drifted one way and smaller ones another. Researchers
had believed that fixed paths were not possible in part
because small particles jiggle constantly, making them
move in uncontrollable ways. Huang discovered that,
with the proper arrangement of pillars, the particles
could be made to slide in a tango-like dance forward
or sideways at each obstacle depending precisely on
the particle's size.
"To suddenly say that there is a deterministic
(non-random) way to do this really flies in the face
of conventional wisdom," said Austin. "It's
something I never would have thought of."
The device could greatly speed up and expand many areas
of biological research and could largely replace some
centrifuge devices that are commonly used to separate
cells and molecules based on mass, according to Cox.
A primary use could be in sorting segments of DNA according
to their length, which is a key step in genome sequencing
efforts. Another use may be in distinguishing one type
of virus from another, because many viruses have a unique
size, slightly different from other viruses, Cox said.
"Right now we use antibodies; we use microscopes;
we sequence the genomes -- there are just a huge number
of heavy-duty 20th century tricks," said Cox. "It
may be that this device will let us say in an instant
that we have one kind of virus and not another."
In pharmaceuticals, the size of the drug particles in
a capsule can play a critical role in how quickly the
drug is absorbed and excreted in the body, noted Sturm.
"You can use advanced chemical engineering methods
to create particles of a certain size, but once you
have done that there is not a lot you can do to filter
out exact sizes and check the quality," Sturm said.
Huang said the device could also result in improved
ink jet printers, which produce better results if the
ink particles are sized precisely.
The researchers are now working to make a tango array
for even smaller particles, including clusters of just
a few protein molecules. It should only be a question
of making a smaller array of silicon pillars, which
is hard but not impossible, said Huang. "So long
as you can make this pattern, you get the same performance,"
The research was funded by the Defense Advanced Research
Projects Agency, the National Science Foundation, the
National Institutes of Health and the State of New Jersey.