186
V. Laxmi et al.
6 Circulating Tumor Cells (CTCs)
Circulating tumor cells (CTCs) in human blood is a connecting link for cancer metastasis. Cancer is a fatal disease and more than 90% of cancer-related deaths are due
to spread of cancer cells from the primary location to other body parts known as
metastasis [125, 126]. Circulating tumor cells detach from primary tumor and start
circulating in blood stream, thus known as circulating tumor cell (CTC). Size of
CTCs range between 16 and 20 μm, and these cells are relatively larger than other
blood cells [9]. CTCs are rare cells as they are present in very low numbers (1–1000
per ml or 1–2 per billion of normal cells) [127]. CTCs also differ from normal blood
cells in biochemical and biophysical properties. CTCs are less stiff and exhibit altered
electrical properties [125]. Current clinical methods of diagnosing cancer are based
on detection of cancer biomarker in serum and radiological imaging of tumor tissues
obtained by liquid biopsy [126]. These methods have low sensitivity and specificity.
Further, repeated performance of biopsy may have adverse effect on the health of
the patient. Also, performing biopsy could be challenging due to limited access to
the tumor location [128].
Separation of CTCs leads to a promising outcome in early detection of cancer
metastasis. Separation of CTCs is a very challenging task due to their rarity in blood.
Like separation of other normal blood cells, centrifugation method is also employed
to isolate CTCs. Fewcett et al. [129] separated cancer cells from peritoneal fluid
using albumin as the floating media. Seal et al. [130] separated CTCs using silicon
blending oil as the floatation medium. In their study, cancer cell is successfully
detected in 53% gastrointestinal tract cancer cell patients sample and 33% breast
cancer samples. OncoQuick is an improved centrifugation technique, in which a
porous barrier is nestled within the 50 ml centrifuge tube to prevent the mixing of
top and bottom layers of the blood sample [131].
Many researchers have reported CTCs separation on microfluidics device based on
their size and surface markers. Size-based separation is also termed as label-free separation, whereas surface markers-based separation is known as label-dependent separation. Size-based separation involve mechanical filtration [126, 132–140], hydrodynamics separation [141–144], dielectrophoresis [145–148], and acoustophoresis
[149]. Surface marker-based methods or label-dependent methods bind CTCs
with cancer-specific antibodies and separate based on surface expression. Labeldependent methods include immune capturing [150, 151], immune magnetophoresis
[152, 153], and deterministic cell rolling [154] to isolate CTCs. The following
paragraph gives a brief discussion on label-free CTCs separation microdevices.
Zhou et al. [137] reported a 3D microfilter membrane, as shown in Fig. 12. The
device comprised of two separable layers, the pores on the top layer are five times
larger than the pore on the bottom membranes. Experiments were performed with
healthy blood spiked with multiple cancer cell lines. A 78–83% separation efficiency with 71–74% cell viability was achieved. The main advantage of the filtration
V. Laxmi et al.
6 Circulating Tumor Cells (CTCs)
Circulating tumor cells (CTCs) in human blood is a connecting link for cancer metastasis. Cancer is a fatal disease and more than 90% of cancer-related deaths are due
to spread of cancer cells from the primary location to other body parts known as
metastasis [125, 126]. Circulating tumor cells detach from primary tumor and start
circulating in blood stream, thus known as circulating tumor cell (CTC). Size of
CTCs range between 16 and 20 μm, and these cells are relatively larger than other
blood cells [9]. CTCs are rare cells as they are present in very low numbers (1–1000
per ml or 1–2 per billion of normal cells) [127]. CTCs also differ from normal blood
cells in biochemical and biophysical properties. CTCs are less stiff and exhibit altered
electrical properties [125]. Current clinical methods of diagnosing cancer are based
on detection of cancer biomarker in serum and radiological imaging of tumor tissues
obtained by liquid biopsy [126]. These methods have low sensitivity and specificity.
Further, repeated performance of biopsy may have adverse effect on the health of
the patient. Also, performing biopsy could be challenging due to limited access to
the tumor location [128].
Separation of CTCs leads to a promising outcome in early detection of cancer
metastasis. Separation of CTCs is a very challenging task due to their rarity in blood.
Like separation of other normal blood cells, centrifugation method is also employed
to isolate CTCs. Fewcett et al. [129] separated cancer cells from peritoneal fluid
using albumin as the floating media. Seal et al. [130] separated CTCs using silicon
blending oil as the floatation medium. In their study, cancer cell is successfully
detected in 53% gastrointestinal tract cancer cell patients sample and 33% breast
cancer samples. OncoQuick is an improved centrifugation technique, in which a
porous barrier is nestled within the 50 ml centrifuge tube to prevent the mixing of
top and bottom layers of the blood sample [131].
Many researchers have reported CTCs separation on microfluidics device based on
their size and surface markers. Size-based separation is also termed as label-free separation, whereas surface markers-based separation is known as label-dependent separation. Size-based separation involve mechanical filtration [126, 132–140], hydrodynamics separation [141–144], dielectrophoresis [145–148], and acoustophoresis
[149]. Surface marker-based methods or label-dependent methods bind CTCs
with cancer-specific antibodies and separate based on surface expression. Labeldependent methods include immune capturing [150, 151], immune magnetophoresis
[152, 153], and deterministic cell rolling [154] to isolate CTCs. The following
paragraph gives a brief discussion on label-free CTCs separation microdevices.
Zhou et al. [137] reported a 3D microfilter membrane, as shown in Fig. 12. The
device comprised of two separable layers, the pores on the top layer are five times
larger than the pore on the bottom membranes. Experiments were performed with
healthy blood spiked with multiple cancer cell lines. A 78–83% separation efficiency with 71–74% cell viability was achieved. The main advantage of the filtration