Biomedical Engineering Reference
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presence of elevated telomerase activity in malignant cells. Such assemblies cause a
change in T2 relaxation time, which can be detected by benchtop NMR
relaxometers. In the absence of such a binding event, the nanoparticle assembly
does not form, and therefore, a change in T2 is not observed. The assay detects
telomerase activity with high sensitivity.
Additional biochemical studies were conducted to establish the potential ofMRS in
detecting cancer related biological compounds. For example in one proof of principle
study, nanoparticles were conjugated with adenosine aptamer and assembled into
clusters [ 33 ]. After administration of adenosine, the nanoparticles disassembled,
with binding to adenosine and a concomitant increase in T2. In another study the
nanoparticles were conjugated to thrombin aptamers and after binding thrombin the
nanoparticles assembled and decreased T2, as imaged by MRI [ 34 ].
In a different study detection of biologically relevant calcium ions was achieved
by using the MRS properties of magnetic nanoparticles [ 1 ]. Calcium has an impor-
tant role as a second messenger in cellular pathways and its detection is important in
investigating neural network activity in the brain. In this study, the nanoparticles
were conjugated to calmodulin, a calcium binding protein. The nanoparticles then
assembled upon binding to intracellular calcium ions. With this clustering event, the
T2 decrease was fivefold greater and detectable by MRI. This outcome suggests
MRS may soon apply to more clinically relevant scenarios.
1.4 Non-invasive MR/SERS Imaging with Gold-Iron Oxide
Nanoparticles
Although MRI is a valuable imaging tool due to its high spatial resolution
(25-100
m), it requires microgram to milligram quantities of contrast agent for
imaging. Therefore, it suffers from low sensitivity. On the other hand, fluorescence
is a sensitive detection method, which suffers from low spatial resolution (2-3 mm)
and background auto-fluorescence. Consequently, a multimodal imaging method
combining MRI and optical detection with sensitivity equivalent to in vivo fluores-
cence but without background interference represents a unique advantage. To that
purpose, combining surface enhanced Raman scattering (SERS) with MRI was
investigated. In SERS, enhanced Raman scattering signal is detected from
molecules absorbed on rough metal surfaces such as gold and silver. SERS is
particularly valuable, since it is highly sensitive (two orders of magnitude brighter
than quantum dots) and the background interference is minimal. The advantage of
SERS over other optical methods is reflected in its capability for spectroscopic
detection and ultra-high sensitivity suitable for identification of single molecules
under certain conditions. It has been shown that in order to obtain an in vivo SERS
signature, intravenous or intramuscular administration of as little as 50 fmol of
SERS active gold nanoparticles is enough to obtain a distinguishing SERS signal
from deep tissues or from tumor xenografts [ 27 ].
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