Inertial Migration of Cancer Cells in a Microfluidic Device - Bioanalysis Advanced Materials Methods and Devices - page 16

2.1 Introduction

The incidence of breast cancer is increasing in many developed countries. In its
diagnosis, it is crucial to detect metastasis or cancer recurrence at an early stage.
The circulating tumor cell (CTC) test has been widely adopted for evaluating the
prognosis of breast cancer [ 3 , 6 , 7 ]. In this test a patient's condition is assessed by
counting the number of cancer cells in a peripheral blood sample. For this purpose,
it is necessary to distinguish cancer cells from other blood cells, and the accuracy of
the CTC test is strongly dependent on the precision of cell identification.
Microfluidic devices for cell separation have received much attention. These
devices can be classified into two groups based on whether the method of separation
is active or passive [ 2 ]. While in active separation an external field is involved, such
as would be caused by magnetic or electric means, in passive separation an external
force is not needed. Passive separation devices have a number of advantages
compared with active separation alternatives; these include miniaturization, inex-
pensive production cost, and easy handling of the device. Examples of passive cell
separation methods are the pillar structures method [ 18 , 21 ], hydrodynamic filtration
[ 23 , 24 ], and biomimetic separation [ 11 , 19 ]. However, despite their high separation
efficiency, devices using such methods are unsuitable for the CTC test because of
their low throughput. To overcome this difficulty, a passive cell separation method
has been investigated which involves inertial migration.
Segre and Silbergerg [ 17 ] originally described the inertial migration process in
1962. When the Reynolds number of a particle is not too small, the inertial force
on it generates a drift velocity perpendicular to the streamline. Hence, a group of
particles flowing in a channel will move towards the sidewalls, and eventually the
particles will be aligned passively at specific positions. Microfluidic devices using
inertial migration have been proposed for separating various rigid particles
[ 1 , 5 , 16 ]. The throughput of this method is very high, because the inertial effect
becomes significant only at high velocities. The time required for particle separa-
tion is often much shorter than that of other methods, and forms its major
advantage.
Recently, some groups have succeeded in applying the inertial migration effect
to the detection or separation of different types of living cells. Kuntaegowa-
danahalli et al. [ 12 ] developed a five-loop Archimedean spiral microchannel and
separated SH-SY5Y neuroblastoma cells (~15

m m in diameter) from C6 rat glioma

cells (~6 m in diameter) in a dilute cell suspension (volume fraction, ~0.05%). In

addition to inertial migration forces, their microfluidic device used the Dean force
generated by the centrifugal effect. The separation efficiency exceeded 80%, with a
high throughput of 1

m

10 6 cells/min. Hur et al. [ 9 ] demonstrated how cells flowing
through channels could be aligned three-dimensionally via the inertial migration
effect. As they focused on cells at a specific depth, the effects of cell overlap and
out-of-focus motion were ignored. Their device allowed red blood cells and
leukocytes to be counted with high sensitivity via image analysis. Using a similar
approach to Kuntaegowadanahalli et al. [ 12 ], Carlo et al. [ 4 ] applied the inertial