Magnetic Nanoparticle

Metrology N

We are developing best practice metrology for characterization of magnetic 

nanoparticle systems (e.g. blocking temperature, anisotropy, property 

ANOMATERIALS

distributions, T1 and T2 relaxation times, hysteretic energy loss, etc.) for use 

in biomedical applications. The emphasis is on the measurement methods 

to enable enhanced MRI imaging, drug delivery, and hyperthermia therapy. 

The tools provided will enable industry to more effectively design and develop 

new magnetic nanoparticles and provide guidelines to the FDA to properly 

compare systems when approving nanoparticle systems for clinical trials.

Objective

Impact and Customers

• Magnetic Resonance Imaging (MRI) is a $60 billion global industry. This imaging method, however, is only 

qualitative. More effective (through better contrast) and quantitative imaging would yield higher rates of detection, 

greater accuracy in detection, and earlier detection of diseases (e.g. cancer, heart disease, etc.) as well as better 

forms of treatment with potentially fewer side effects.

• Drug delivery and hyperthermia therapy for cancer treatment are still in the preclinical stages, but our input has 

the potential to significantly optimize the design and development of nanoparticles for these applications by 

eliminating the costly empirical approach currently used. This will help reduce the $1.7 billion price tag to bring 

a drug to the market.

Approach

Materials Science and Engineering Laboratory

Optimization of magnetic nanoparticle synthesis for a specific biomedical application 

necessitates a solid understanding of both fundamental magnetism and its 

measurement. Since most pharmaceutical companies employ biologists and chemists 

without such knowledge, we will aim to develop an ASTM standard for their use, applying 

established bulk and thin film techniques to nanoparticle systems for determining the 

appropriate magnetic properties of both individual and collections of nanoparticles. 

In addition, two new measurement techniques will be developed: First Order Reversal 

Curve (FORC) models to correlate physical size distributions with magnetic property 

distributions, and transverse AC Susceptometry for determining interaction timescales 

for individual and collective systems.

There are also specific requirements for each medical application. For example, a 

novel variable field and frequency relaxometer will be developed for correlating the 

materials structure with T1 and T2 relaxation times to develop stable T1 and T2 SRMs 

for quantitative MRIs. For hyperthermia therapy, a microcalorimeter will be developed 

for accurately measuring temperature changes in a nanoparticle suspension under the 

influence of a high frequency alternating magnetic field.

855-11-14b
Materials Science and Engineering Laboratory

We recently determined that strongly 

interacting coated magnetic nanoparticles 

yield very large increases (by a factor 

of seven) in heat output as compared 

to nominally identical particles which 

are only weakly interacting, illustrating 

the enormous consequences of using 

improperly characterized nanoparticles 

for hyperthermia treatment. This behavior 

was found in two nanoparticle systems 

which were nominally identical physically 

(as determined by photon correlation 

spectroscopy, transmission electron 

microscopy, Mössbauer spectroscopy, and 

x-ray diffraction), and were very similar 

magnetically (although the nanoparticle 

system with the larger heating rate had 

the smaller saturation magnetization). 

The difference between the nanoparticle 

systems, identified through small angle 

neutron scattering, was the interaction 

radius, which was modified by changing 

the dextran stabilization layer. The more 

closely spaced nanoparticles interacted 

more strongly, utilizing a collective behavior 

to enhance the heating properties. This 

finding is a significant departure from 

“common knowledge” in the medical 

community, which has long contended that 

non-interacting magnetic nanoparticles 

are the ideal material for hyperthermia 

treatment.

Typically, conventional magnetic 

characterization methods reveal information 

about the “bulk” properties of a material. 

However, when combined with physical 

characterization methods like transmission 

electron microscopy (TEM), the same 

magnetic characterization methods can be 

used to separate and probe the details of 

magnetic nanoparticle growth and aging 

in a manner that neither technique can do 

alone. Recently, through this combination, 

we were able to determine the intermediate 

stage in Co nanoparticle growth to be 

Co cluster complexes formed with the 

surfactants. Meanwhile, after synthesis, 

a hysteresis loop shift along the field axis 

(exchange bias) is observed for the aged 

Co colloid, indicating the formation of antiferromagnetic/ferromagnetic (AFM/FM) 

interfaces in the aged Co nanoparticles. 

Although not measurable by x-ray 

diffraction, high-resolution TEM results 

confirm that a thin and inhomogeneous 

AFM face-centered cubic cobalt (II) 

oxide (CoO) grows on the surface of the 

FM Co nanoparticles, a configuration 

which is not sufficient by itself to produce 

exchange bias. This suggests that not only 

the AFM/FM coupling in individual aged 

nanoparticle matters, but also the strong 

magnetostatic coupling between the 

neighboring nanoparticles contributes to 

the exchange bias observed.

We recently demonstrated (with the help 

of SURF student Christine Lau) one effect 

of thermal, chemical, and/or mechanical 

processing on magnetic nanoparticles: 

the processing causes an expansion of the 

crystal lattice which in turn changes the 

bond angles between different elements 

in the Fe3O4 structure. This appears to 

partially change the magnetic coupling 

from ferromagnetic to antiferromagnetic, 

reducing the saturation magnetization. 

This had been observed previously in 

magnetite thin films, but never before in 

nanoparticles, and may be one origin 

of the significant variation in saturation 

magnetization of Fe3O4 nanoparticles 

from the bulk.

Accomplishments

Robert Shull

Guangjun Cheng (Physics)

Angela Hight Walker (Physics)

Julie Borchers (NCNR)

Andrew Jackson (NCNR)

Cindi L. Dennis

(Metallurgy Division)

(301) 975-6041

cindi.dennis@nist.gov

www.nist.gov/metallurgy

Learn More Publications

Dennis CL, Jackson AJ, Borchers JA, Ivkov R, Foreman AR, Lau JW, Goernitz E and Gruettner C The 

Influence of Collective Behavior on the Magnetic and Heating Properties of Iron Oxide Nanoparticles

Journal of Applied Physics, 103: 07A319 (2008)

Dagata JA, Farkas N, Dennis CL, Shull RD, Hackley VA, Yang C, Pirollo KF and Chang EH Physical 

Characterization Methods for Iron-oxide Contrast Agents Encapsulated Within a Targeted Liposomebased Delivery System Nanotechnology, 19: 305101 (2008)

Dennis CL, Jackson AJ, Borchers JA, Ivkov R, Foreman AR, Hoopes PJ, Strawbridge R, Pierce Z, Goernitz 

E, Lau JW and Gruettner C The Influence of Magnetic and Physiological Behavior on the Effectiveness of 

Iron Oxide Nanoparticles for Hyperthermia Journal of Physics D: Applied Physics, 41:134020 (2008)

Dennis CL, Cheng G, Baler KA, Maranville BB, Hight Walker AR and Shull RD The Influence of 

Temperature on the Magnetic Behavior of Colloidal Cobalt Nanoparticles IEEE Transactions on 

Magnetism, 43:2448 (2007)

Small angle neutron scattering data showing 

interactions.

TEM image of Co nanoparticle, with dotted lines 

showing location of CoO patches.

Saturation magnetization data vs. change in lattice 

constant.