Page 234 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

9.3 Microfluidic systems in cancer 233

13. improvement of reproducibility.
14. eliminating the need for skilled technicians.
15. enabling smooth and predictable transport of materials through the device via
laminar flow because of narrow channels and preventing turbulent flow.
By contrast microfluidic technology usage for modeling purpose have some limi-
tation [21]:

1. if subsequent biochemical studies are needed retrieving cells from microfluidic
devices is possible but not straightforward.
2. If a large number of cells are required for downstream biochemical studies
or if secreted proteins should be quantified, the low cell number can also be a
drawback.
3. because device materials in terms of mechanical properties (e.g., typically
PDMS or glass coverslip) are much stiffer than the typical hydrogels in which
cells are embedded, might also constitute an issue for some 3D studies. Hence,
only cells that are far from the PDMS or glass surfaces should be analyzed.
4. PDMS can adsorb small hydrophobic molecules and it can cause problems for
drug screening studies.
5. lack of organ specificity is the current limitation of in vitro metastatic models.

9.3 Microfluidic systems in cancer
The obvious potential of microfluidic technologies to help the advance of cancer
research has been characterized. They are especially important in metastatic cascade
studying, due to the manner of metastatic spread that occurs through several steps and
it is difficult to resolve them in vivo. Containing metastasis by conventional therapies
have limited success and it causes 90% of cancer-related deaths. Intravital imaging
is so useful in metastasis study [49,50], but it needs specialized expertise and equip-
ment. As well, in several visceral organs because of their deep location, access to
high image resolution is hard [21]. In addition, some events of the metastatic cascade
such as intravasation are rare and hard to image in vivo, but this rate of occurrence
can be more readily modulated in vitro. Each step of the cascade represents a prom-
ising target for therapeutic intervention. Progression of solid tumors can be divided
into steps, include an epithelial-to-mesenchymal transition (EMT), invasion, intrava-
sation, transport of circulating tumor cells (CTCs) in the bloodstream, extravasation
in the distant organ, and recolonization at the metastatic site [51]. Microfluidic assays
have been designed to repeat definite features of some of these steps, such as EMT
[52], cancer cell invasion and adhesion [53], intravasation and extravasation [54,55].
In vitro metastatic models have some limitations that lack of organ specific-
ity is one of the main current limitations. The importance of this issue is because
there are developing evidence that shows cancer cells relate to their microenviron-
ment [21], particularly with organ-specific cells which leads to organ selectivity in
metastasis [56]. Therefore, targeted therapeutic approaches for inhibiting metastasis