Magnetics Business & Technology - Summer 2018 - 6

FEATURE ARTICLE

Magne c Nanopar cles Leap from Lab
Bench to Breast Cancer Clinical Trials
Longstanding Sandia, industry collabora on
produces precise par cles

the ingredients and heat the mixture to about 650 degrees Fahrenheit. How quickly the heat increases determines the nanoparticle size, said Huber. However, just like your oven at home, it
will overshoot the critical temperature and then cool down until
it levels off. How much the temperature overshoots this critical
temperature also affects the size, producing nanoparticles more
than 15 percent larger or smaller.

Sandia National Laboratories materials chemist Dale Huber has
been working on the challenge of making iron-based nanoparticles the exact same size for 15 years.
Now, he and his long-term collaborators at Imagion Biosystems
will use these magnetic nanoparticles for their first breast cancer
clinical trial later this year. The nanoparticles stick to breast
cancer cells, allowing the detection and removal of even small
metastases.
Imagion Biosystems and Huber have been working together
synthesizing nanoparticles since the opening of the Center for
Integrated Nanotechnologies in 2006.
"Having access to the talent pool at CINT with experts like Dale
Huber has been helpful," said Bob Proulx, CEO of Imagion
Biosystems. "Additionally, the fact that CINT has a user program
that allows industry to access the facilities and equipment that,
otherwise, would be too expensive for a small company like ours
was valuable. The initial work we did with CINT to develop a
method to give precise control over the size of the nanoparticle
was key for our MagSense magnetic relaxometry technology for
the detection of cancer."
CINT is a user facility jointly operated by Sandia and Los Alamos
National Laboratory for the U.S. Department of Energy's Office
of Science. CINT provides free access to state-of-the-art equipment and world-leading scientists for nanoscience researchers
in academia and industry, provided they publish the results in
scientific journals.
The magnetic nanoparticles are coated with cancer antibodies, which stick specifically to cancerous cells. A tiny magnetic
pulse - about the strength of a refrigerator magnet and hundreds
of times weaker than one produced by an MRI machine - can
sense the difference between nanoparticles stuck to cancer cells
and those that are floating freely, allowing the detection of very
small metastases.

Precision synthesis of magnetic nanoparticles
However, for Imagion Biosystems' cancer detection method to
work, all the nanoparticles have to be almost exactly the same
size.
"A 2 percent variation is the difference between perfect and just
about useless," said Huber. He added laughing, "It was eye
opening for me and if had I known that in the beginning, I might
not have taken on the challenge."
Erika Vreeland, who worked with Huber during her doctoral
thesis to develop reproducible synthesis and was hired by
Imagion Biosystems to be their chief nanoparticle scientist after
she graduated said, "We eliminated all of the witchcraft of the
reaction."
The standard method to make iron nanoparticles is to combine

Magnetics Business & Technology * Summer 2018

Transmission electron microscopy images of the diﬀerent sizes of
nanoparticles Dale Huber can make by varying the synthesis time
(Image courtesy of Sandia National Laboratories). The nanoparticles
range from a) 9 nm to h) 35 nm.
Instead, Vreeland and Huber developed a method where they
slowly add the ingredients to a molten metal bath whose temperature varies less than half a degree. This produces nanoparticles with less than 2 percent size variation. Huber said, "It's not
the easiest way to make particles, but that's why they're so much
better."
Not only did the team discover a highly reproducible method to
make the tiny particles, they also transferred the process twice
- once to Imagion and once to ChemConnection, a nanoparticle
manufacturer in the Netherlands that can make the nanoparticles
under the strict U.S. Food and Drug Administration and European Union regulations needed for use in patient clinical trials.
"The synthesis was transferred to the lab in the Netherlands
while maintaining size control," said Huber. "This is huge. Everything changes, even the boiling points, because the Netherlands

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