(164g) Enhancing Microfluidic Capture of Circulating Tumor Cells Using Magnetic Nanoparticles

Majority of cancer deaths are attributed to metastasis,
the translocation of primary tumor cells to secondary sites. Circulating tumor
cells (CTCs), cancer cells found in the blood stream, are believed to be a
major contributor to metastasis. Hence, enumeration of CTCs holds promise as a
means of monitoring disease progression. Unfortunately, the extreme rarity of
CTCs in blood samples (typically ~1 CTC per 10⁶ blood cells) makes
accurate enumeration challenging. The use of microfluidic devices
functionalized with antibodies to capture and enumerate CTCs has been an active
area of research for over a decade. In these devices one or more surfaces are
typically coated with an antibody against the epithelial cell adhesion molecule
(EpCAM), which is believed to be a biomarker for CTCs. Such microfluidic
devices can reliably count the number of CTCs in blood samples at low flow
rates, but the desire to increase throughput from current values of 2-3 mL/hr leads
to loss of specificity towards CTCs. Furthermore, many non-CTC cells are captured
in these devices, resulting in poor capture purity. Here we explore the
possibility of enhancing the capture efficiency and specificity of microfluidic
CTC capture and enumeration systems through the use of magnetic nanoparticles in
the presence of a magnetic field gradient to improve cross-stream migration of
cells towards the antibody (ab) functionalized surface of the
microfluidic channels. Initial studies have focused on demonstrating this
principle using cells that have uptaken nanoparticles through non-specific
interactions.

First we studied the uptake of dextran coated magnetic
nanoparticles by EpCAM-expressing BxPC-3 pancreatic cells. Then capture
efficiency for these cells using a microfluidic device with herringbone
structure was quantified at 2 uL/s for the cases of bare and
antibody-functionalized devices with and without magnetic fields. In the case
of microfluidic devices coated with anti-EpCAM, in the presence of an external
magnetic field created using a Halbach Array (HA), 62 % capture efficiency was
found as opposed to 43 % when the device was not subjected to external magnetic
field. We have currently obtained magnetic nanoparticles that can be employed to
enhance the capture of CTCs at a throughput of 7.2 mL/hr.

Ongoing studies aim to develop magnetic nanoparticles
conjugated with a peptide specific to EpCAM expressing BxPC3 cells. We expect
such specific targeting will lead to an even greater improvement in capture
efficiency and selectivity, especially in complex whole blood samples.