Biomedical Engineering Reference
In-Depth Information
nanobeads, and the taller peak at high frequency arises from, and gives a measure
of, the number of free beads. According to Stromberg
et al.
, the samples can be
discriminated as being positive or negative for target DNA sequence by measuring
the level of m
(emu g
− 1
) at the high-frequency peak (i.e., at the Brownian relaxation
frequency for the free beads), while the concentration of RCA coils can be deter-
mined down to the p
M
range from the magnetization spectrum [56]. Sample
preparation, RCA times, nanobead surface coverage with oligonucleotides, and
other aspects of the experimental protocol still require optimization. Nonetheless,
with a view towards developing this into a point-of-care diagnostic device, the
authors have proposed that if suffi ciently small beads were used it would be pos-
sible to detect the magnetic signal at a suffi ciently high frequency where the
intrinsic voltage noise of the sensor (white noise) would be minimal. This detec-
tion principle, based on Brownian relaxation frequency, has also been demon-
strated in the case of antigen- antibody binding [60] .
″
5.7
Detection of Circulating Tumor Cells
The most notable success of the application of magnetic nanoparticles in
in vitro
diagnostics has been in the commercialization of the CellSearch System by
Veridex, LLC, for monitoring disease progression in patients with metastatic
breast, colorectal, or prostate cancer [61]. The CellSearch System is being pro-
moted as a powerful tool for measuring the number of circulating tumor cells
(CTCs) in the blood to derive prognostic information. The system involves enrich-
ing for CTCs using ferrofl uid (colloidal fl uid of magnetic nanoparticles coated with
antibodies targeting the epithelial cell adhesion molecule); in this way, tumor cells
of epithelial origin can be magnetically separated from the bulk of the cellular
material within the blood sample. The CTCs are then stained with mAbs against
cytokeratin, the intermediate fi laments of epithelial cells. In order to distinguish
contaminating leukocytes from CTCs, a pan-leukocyte mAb against CD45 is also
used to stain the cells. An external magnetic force is applied to pull the cells to
the surface of the cartridge that contains the sample, and to hold the cells in place
at a single focal depth. These cells are then scanned by the fl uorescence optical
system, and the images of fl uorescence events presented to the user for classifi ca-
tion of the cells: CTCs are positive for cytokeratin, but negative for CD45. When
using this CellSearch System, it is possible to detect just a few CTCs per 7.5 ml
of blood. Moreover, the results of clinical studies have shown that, in patients with
metastatic breast cancer, the presence of more than fi ve CTCs per 7.5 ml of blood
is prognostic of a short progression-free survival and short overall survival [62].
Magnetic nanoparticles have tremendous potential to be developed into various
platforms for the enrichment and detection of CTCs in the peripheral blood of
patients with cancer, and this has enormous clinical implications for the monitor-
ing and treatment of cancer patients. Recent studies have shown that CTCs are
present in 30% of patients with early-stage breast cancer, and in over 50% of those
