
This animation demonstrates a technique that uses a magnetic field
to selectively separate tiny magnetic particles using an array of
metal disks, representing a highly sensitive method for
potentially diagnosing disease by testing samples from patients. (Animation:
35 seconds)

Changing the speed of a rotating magnetic field can be used to
separate yeast particles with an experimental technique that
selectively separates tiny magnetic particles using an array of
metal disks. (Animation:
28 seconds)
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As the magnetic field rotates, the particles
move from one disk to another until they are separated from the rest
of the sample. Rotating the magnetic field at specific speeds
separates only particles of certain sizes, meaning pathogens attached
to those particles would be separated from the sample by varying the
rotation speed, Lee said.
In recent experiments, samples containing magnetic particles attached
to yeast were placed inside the rotating magnetic field and separated
from the rest of the samples. Findings are detailed in a research
paper appearing online this month in Lab on a Chip magazine and in the
December print edition of the publication. The paper was written by
assistant professor Benjamin Yellen, graduate students Randall Erb and
H. Son, and undergraduate student R. Hewlin Jr., all from Duke
University's Department of Mechanical Engineering and Materials
Science, and postdoctoral fellow Hao Shang and Lee, both from Purdue's
School of Chemical Engineering and Weldon School of Biomedical
Engineering.
The technique, called non-linear magnetophoretic separation, works
using an array of disks made of cobalt and coated with chromium to
prevent corrosion. The disks are regularly, or periodically, spaced on
the surface of the silicon chip.
An advantage of the non-linear magnetophoresis technique is that it
can be used to simultaneously separate and identify pathogens with a
sensitivity up to a million times higher than the "solid phase
immunoassays" commonly used today for human diagnostics, said Shang,
co-founder of MagSense Life Sciences Inc. and a research scientist at
the company, located at the Purdue Research Park. The company is
developing a new method to produce the magnetic particles.
The biotechnology industry currently uses
magnetic particles to make drugs by separating components in
biological materials. The particles attract specific types of
molecules, such as proteins and DNA, and then a magnet is used to
separate them from the rest of the sample.
The new approach, however, aims to use the particles not for research
but for medical diagnostics or possibly to detect biological materials
in environmental samples.
The micron-size magnetic particles, which are made of thousands of
nanometer-size particles, have a property called superparamagnetism.
This means the particles are not magnetic unless they are in a
magnetic field, so they can be mixed in a solution without attracting
each other and clumping together, which is critical for them to be
distributed uniformly throughout the solution. But as soon as the
rotating magnetic field is applied, the particles become magnetic,
which enables them to be separated.
"What some people are doing very successfully is attaching antibodies
that recognize pathogens like bacteria and viruses to these magnetic
particles," Lee said. "One of the things we've been working on for
quite a long time is to identify many different pathogens
simultaneously."
Such an innovation represents a powerful new tool for medical
diagnostics.
"When you walk into a doctor's office, the problem is that it could be
one of five or six different pathogens giving you the symptoms," Lee
said. "The doctor cannot determine which pathogen you have, so they
simply give you a broad-spectrum antibiotic or tell you to go home and
get some rest. There clearly is a need for technology that can
recognize multiple pathogens simultaneously and at very low levels. It
is likely they will be chip-based technologies that are easy to
implement in medical environments."
The particles are said to move in a "non-linear" fashion because their
motion does not simply increase as the speed of the rotating magnetic
field increases.
"There is a surprising effect where at some point the particles stop
moving due to their size or what they are attached to, and we can use
this effect to our advantage," Lee said. "This effect will allow us to
quickly sort through a million particles and say that one's got a
certain bacterium on it, that one's got a virus on it, and so on."
The disks are aligned so that their poles point in the same direction.
The particles are drawn across the chip as they are attracted by the
magnetic fields emanating from the poles and resulting from the
external rotating magnetic field.
Different size particles have different "critical frequencies," which
means they are moved across the chip by rotating the external magnetic
field at specific speeds matching those frequencies.
"So, at a certain frequency, you will see larger particles moving and
smaller particles just sort of jitter back and forth," Lee said.
This frequency is higher for larger particles than it is for smaller
particles, so speeding up and slowing down the rotation of the
external magnetic field causes particles to move based on their size.
"Say we would like to sort out 50 different magnetic particle sizes,
and we could put a different antibody on each one," Lee said. "Then
each one would react with a different pathogen. It might have one for
dengue virus, one for West Nile virus, and that way I could add them
to a blood sample from a patient and sort them out within two minutes."
Lee's work is based at the Birck Nanotechnology Center at Purdue's
Discovery Park. The research has been supported by the Institute for
Nanoelectronics and Computing, funded by NASA and located at Discovery
Park. Hewlin's participation as an undergraduate was supported by the
National Science Foundation.
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