Page 10 - Read Online

Su et al. J Cancer Metastasis Treat 2020;6:19 I http://dx.doi.org/10.20517/2394-4722.2020.48 Page 5 of 21

Fabrication of microfluidic channels
Poly(dimethylsiloxane) (PDMS) is the most commonly employed material in the fabrication of the
microfluidic channels since it is low-cost, chemically inert under most circumstances, nontoxic, and
[29]
compatible with lithography processes . Conventional 2D microfluidic channels can be made by a soft
lithography process. A master mold is firstly fabricated by photolithography, followed by the curing of
PDMS on it. Due to the low surface free energy and elasticity, the cured PDMS can replicate the shape
of the master mold and be released without causing any damage. Both reversible and irreversible sealing
[30]
can be realized between PDMS and the channel substrate . Reversible sealing can be achieved either
by applying a pressure greater than 5 psi or through adhesive tapes, while irreversible sealing can be
[31]
formed by plasma treatment of the contact surface . Despite the straight-forward fabrication processes,
many challenges exist for the PDMS microfluidic channels based on soft lithography, such as flow profile
problems due to leakage and uneven pressure, low fabrication efficiency, and poor flexibility due to the
need of fabricating the master molds.

There has been much progress in developing both novel materials and fabrication technologies for the
microfluidic channels [32,33] . The ability to manufacture 3D structures and the additive nature of the process
have made 3D printing a promising candidate in the fabrication of microfluidic channels. A polyjet-based
[34]
3D printed fluidic device was developed by Gross et al. . The device design was completed with the aid
of computer-aided software and then converted to a STL file prior to printing. A rigid and transparent
channel was developed with precise control of the channel dimension (1 mm × 0.8 mm × 2 mm). Besides
[35]
3D printing, other techniques have also been explored to fabricate 3D microfluidic channels. Song et al.
proposed a metal wire removal process, where a thin soldering wire with a 3D circular shape was
employed. After pouring PDMS onto the metal wire and curing it, the metal wire was melted out via
heating. With this simple process, circular, helix-shaped, and double helix-shaped microfluidic channels
can be easily prepared. In another work, a direct laser writing approach was used to prepare microfluidic
channels embedded in fused silica with an aspect ratio over 1000 . Direct laser writing usually results in
[36]
high surface roughness. In this work, wet etching and glass drawing process were conducted after the laser
writing, which significantly reduced the surface roughness from 50.3 nm to 0.29 nm.

Microfluidic channels in magnetic separation
The design of microfluidic channels play an important role in optimizing the efficiency of magnetic
[37]
separation. Inglis et al. fabricated a device with ferromagnetic Ni strips underneath the separation
chamber at angle of 10° to the bottom of the continuous flow [Figure 2A]. When an external magnetic
field is applied, the flux lines are concentrated on the Ni strips. Magnetically labeled cells [in this case, the
white blood cells (WBCs)] deviate away from the flow direction and move along the direction of the strips.
In this way, they achieved separation of WBCs from red blood cells (RBCs). In another technique, Hans
and Frazier applied a uniform magnetic field normal to the ferromagnetic Ni wires which was fabricated
[38]
along the length of the microfluidic channel . They magnetically deformed the ferromagnetic wire using
high magnetic field gradient, which generates the magnetic field gradient. By playing around with the
direction of the magnetic field, they got the fabricated device to work in “diamagnetic capture mode” and
“paramagnetic capture mode” that very efficiently separated the diamagnetic WBCs, cells and tissues, and
the paramagnetic deoxy-hemoglobin RBCs.

Afshar et al. designed a system to meet the requirements of specific bioassays to study the on-chip
[39]
agglutination assays for the detection of rare analytes by particle coupling as doublets. They integrated
the PDMS microfluidic channels with soft magnetic microtips of varied shapes and sizes to provide
the magnetic field gradient for the particles. The magnetic tips serve as the field concentrators and are
positioned in the near vicinity of the microfluidic channel to generate even higher magnetic actuation
forces. This device was experimentally tested to achieve three goals with two sets of superparamagnetic