Page 227 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

226 CHAPTER 9 Application of microfluidics in cancer treatment

combinations, monitoring cellular responses, study of cellular, tissue and total-body
behavior upon irradiation, microbubbles production, etc. [19,20]. Also microbubbles
can be used in gene therapy and as a drug delivery vehicle for cancer treatment
through antivascular effects [20]. In order to therapeutic targets finding and new drug
testing for cancer, diverse experimental models of types in vivo, ex vivo, and in vitro
have been traditionally employed [21].
Microfluidic devices provide highly controlled environments and that can be
configured in different cell-culture formats such as single-cell culture and auto-
matic cell culture [19]. In vitro cell culture with microfluidic devices, provides a
high temporal resolution in single-cell level quantification of cellular responses to
different stimuli. Microfluidic technics have been utilized to look at linear DNA
specifically using restriction endonucleases. The fragments of DNA within the
microfluidic channels can be functionalized with fluorescent proteins. By these
technics, the analysis of how control of DNA modifications, the genetic contents of
DNA, and the sizes of DNA fragments via proteins using small volumes of analysis
is possible [22].
Immunoassays are another of technic which has been optimized by micro-
fluidic. Immunoassays are used to measures the presence or concentration of a
macromolecule or a micromolecule in a solution by using a tagged antibody or
an antigen which emits a detectable signal. Recently, microfluidic methods have
been developed to optimize this time-consuming process, by shortening the reac-
tion times and washing steps [22]. The polymers such as polydimethyl sulfoxide
(PDMS), molecules such as self-assembled monolayers (SAM) have been used for
the fabrication of microchannels to functionalize substrates with certain chemi-
cal compounds to immobilize proteins, DNA or cells [23,24]. For example, the
microchannels are made of PDMS which would minimize the diffusion distances
by replenishing the diffusion layer with molecules [25]. Multivalent ligand binding
studies have been performed by using a PDMS glass/microfluidic chip. Supported
lipid vesicles with the incorporated ligand were analyzed within these channels.
The lipid compound 2,4 dinitrophenyl (DNP) was fused onto the glass surface to
form a continuous lipid bilayer. First, a fluorescently labeled anti-DNP with pre-
determined concentrations were injected into these microchannels. Then by using
total internal reflection fluorescence microscopy (TIRFM) the surface-bound anti-
bodies were imaged [25].
The PDMS microchannels with good biocompatibility have been applied for
cell-based assays. For example, PDMS was constructed with two inlets and various
staggered channels which were used as chaotic mixers to serially dilute the mol-
ecules which are connected to the main channel. A PDMS gradient generator was
employed to study the effects of chemotaxis. To monitor cell migration, the concen-
tration gradients of interleukins were administered onto a neutrophil substrate at the
main channel. The migratory characteristics of the neutrophil shifted to the region
of the highest gradient of interleukins [25]. Also the PDMS is used to control fluid
flow for deposit cells and proteins onto the microfabricated channels. The criteria of
microfluidic cell separation technology are listed in Table 9.2.