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3D-printing and microfluidics
3D-printing’s unique ability to monolithically create 3D membrane were 5 mm and 100 µm, respectively. The
structures to realize true 3D microfluidic architectures membrane would deflect by ~200 µm under 2.9 psi
that were unattainable by the traditional microfabrication pressure. Due to the large Young’s modulus, the size of the
techniques. Lee et al. fabricated a helical channel using membrane was considerably larger than the PDMS-based
SLA for inertia-based bacteria separation (Figure 1). valve to achieve the required deflection for valve closure.
The helical channel spiraled up in the z-direction and A similar circular membrane valve was demonstrated by
formed a true 3D microchannel with a trapezoid cross- Gong et al. By pushing the thickness of the membrane
[34]
section . The 3D helical design significantly reduced down to ~20 µm, they were able to reduce the diameter
[27]
the device footprint compared to the planer spiral design. of the membrane to ~1 mm and pack the valves into a
Shallan et al. used a liquid resin-based 3D printer to dense array. The required diameter of the membrane in
fabricate 3D microchannels for more efficient passive the valve at various membrane thickness was studied
mixing . Monaghan et al. developed a 3D microfluidic by Rogers et al. The same design was also used as
[35]
[28]
device coupled with optical fibers to monitor chemical an active Micropump in 3D-printed microfluidics .
[34]
synthesis . The group used the same approach to fabricate A 3D-printed Quake valve was demonstrated by Keating
[29]
a 3D tree-like chemical gradient generator with reduced et al. using an inkjet-based technique that is capable of
footprint and high portability . Cabot et al. used a printing multiple materials . Tangoplus, a rubber-like
[28]
[36]
similar 3D-printed microfluidic passive mixer to improve flexible material was used to print the membrane while
sample mixing in a capillary electrophoresis assay that other parts of the microfluidic device were printed with
measured the pK a [30] . A highly complex interconnected rigid plastic material. Nonetheless, Tangoplus was less
3D microfluidic network was fabricated by casting epoxy flexible than PDMS, and the dimension of the control
or agarose against a 3D-printed sacrificial mold . After channel was in the millimeter range. In addition to active
[31]
casting, the mold made of isomalt was dissolved to clear valves, passive valves were also created in 3D-printed
space for microfluidic channels. 3D-printing also enabled microfluidic devices. These were usually one-way check
easy integration of chip-user interface that coupled the valves similar to those in silicon-based MEMS device.
external fluid into the microfluidic chip. A good example Sochol et al. printed microfluidic circuitry components,
was demonstrated by Anderson et al. who fabricated a such as fluidic diodes and transistors, by incorporating
microfluidic drug screening platform that incorporated these designs . Chen et al. incorporated these passive
[37]
standard membrane devices for the cell culture and valves to prevent backflow in a 3D-printed microfluidic
standard thread fitting for the coupling of tubing . multi-chamber cell culture device that modeled the
[32]
Another example was demonstrated by Au et al. who circulatory system .
[38]
printed a Luer lock fitting on the microfluidic device as a Another enhancement brought to microfluidics by
standard fluid connector . 3D-printing is device modulation. With 3D-printing
[33]
One of the reasons for PDMS being so popular in technology, it is straightforward to fabricate individual
microfluidics is due to its high flexibility that enables modules, each of which contains a single microfluidic
the fabrication of multilayer pneumatic valves and component and to incorporate standard connectors on
pumps. Each multilayer pneumatic valve consists of the individual modules for easy assembly. Bhargava
two overlapping crisscross microchannels separated by et al. 3D-printed cubes with a female port and a male
a thin PDMS membrane at the intersection. One of the connector (Figure 3) . These cubes, which functioned
[39]
microchannels carries the sample fluid, and the other one as microfluidic modules, created elastic reversible
carries the control fluid (sometimes just air). When the liquid-tight seals when coupled together. Microfluidic
control channel is pressurized, the thin PDMS membrane components, such as straight channels, helical channels,
deflects, creating a bulge that blocks the fluidic channel. and reaction chambers, were embedded in these modules.
The enabling factor of the multilayer pneumatic valve Non-fluidic components, such as optical components,
is the low Young’s modulus of PDMS, which allows were also introduced into individual modules. A fully
the thin membrane to deflect easily. In contrast, most functional 3D microfluidic network was constructed
3D-printed plastic materials have Young’s modulus by plug-and-play. Lee et al. developed a 3D-printed
hundreds or thousands of times larger than PDMS, which modular microfluidic system assembled together with
makes it difficult to pneumatically deflect the 3D-printed horseshoe-shaped pins that functioned somewhat like a
membrane. Nevertheless, using relatively flexible plastic, stapler bullet . To prevent leakage, O-rings were used
[40]
active valving has been demonstrated in a 3D-printed at the fluidic interface between the modules. Nie et al.
monolithic microfluidic device (Figure 2). In this work, designed lego-like microfluidic modules with press-fit
Au et al. printed a multilayer membrane valve using connectors along the edge of each modular block. Due
watershed (a biocompatible resin) with Young’s modulus to the poor sealing, this system was only designed for
of 2.7 GPa . The diameter and thickness of the circular capillary-driven flow and could not operate under high
[20]
64 International Journal of Bioprinting (2019)–Volume 5, Issue 2

