Biomedical Engineering Reference
In-Depth Information
1.2
Superparamagnetic Nanoparticles
The properties of nanoparticle reagents make possible the unique characteristics
of MRSw biosensing. To date, all MRSw demonstrations have used some type of
superparamagnetic iron oxide (SPIO) particle. The earliest iron oxide particles
were utilized for localized lymph node heating over 45 years ago [13]. SPIO
nanoparticles contain one or more superparamagnetic iron oxide cores composed
of a mixture of magnetite (Fe
3
O
4
) and maghemite (
- Fe
2
O
3
), which have similar
magnetic properties. These iron oxide cores, which typically are less than 14 nm
in diameter, are encapsulated in a hydrophilic monomer or polymer coating so as
to endow water solubility [14]. When magnetite crystals are oxidized, the crystal
lattice changes from the inverse spinel of magnetite to the cubic Fe(III) oxide
lattice of maghemite [14]. SPIO particles are distinguished from paramagnetic
particles in that their small iron oxide cores are comprised of single- domain mag-
netic crystals, the magnetic moments of which readily align with an external
magnetic fi eld, and this results in a microscopic dipolar magnetic fi eld surround-
ing the iron crystal. Upon removal of the external magnetic fi eld, the magnetic
moments of these cores randomize, leading to a complete dissipation of the
induced magnetic fi eld [14, 15]. The magnetization and magnetic susceptibility of
SPIO nanoparticles are much larger than that of paramagnetic ions and bioinor-
ganic complexes of iron, such as ferritin [16].
Depending on the method of synthesis, SPIO particles can range in size from
γ
∼
2 nm (citrate-inhibited growth), tens of nanometers (polymer-coated), to microm-
eters [14]. SPIO are typically categorized based on their overall diameter, which
includes the metal core and organic coating [14]. SPIO particles between 300 nm
and 3.5
m are referred to as oral-SPIO because they were fi rst used for
in vivo
imaging via oral delivery, such as the silane-coated contrast agent ferumoxsil (trade
name GastroMARK ® ) [17] . Like most particles larger than 50 nm, oral - SPIOs
contain more than one iron core per particle. Over a matter of minutes, however,
a solution of oral-SPIO particles can settle due to their large size [18], which com-
plicates their use for the aggregation-based sensing used by MRSws. In order to
circumvent this, MRSw applications using oral-SPIOs have utilized surface treat-
ments to provide adequate buoyancy to the particles, such that they do not settle.
In addition, timed mixing steps with rapid measurements have been used to
ensure a reproducible suspension of the particles during measurement [19, 20].
Particles which are slightly smaller than oral-SPIO particles are referred to as
standard SPIO (SSPIO) nanoparticles, and have hydrated diameters of 60-150 nm.
As with oral-SPIO, these particles contain more than one iron core per particle. A
solution of these particles does not settle, although under certain conditions they
may aggregate when placed in a magnetic fi eld [18] - a property which is used for
magnetic separations by SSPIO (examples include those produced by companies
such as Miltenyi Biotech). A similar, fi eld-dependent aggregation has also been
observed for oral-SPIO [21-23], and can be used for the sensitivity enhancement
of MRSw biosensors [19]. However, the application of these particles to MRSw
μ
