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PII: S0167-9317(17)30407-0
DOI: https://doi.org/10.1016/j.mee.2017.12.010
Reference: MEE 10682
To appear in: Microelectronic Engineering
Received date: 15 June 2017
Revised date: 14 December 2017
Accepted date: 16 December 2017
Please cite this article as: Ryan D. Sochol, Eric Sweet, Casey C. Glick, Sung-Yueh Wu,
Chen Yang, Michael Restaino, Liwei Lin , 3D printed microfluidics and microelectronics.
The address for the corresponding author was captured as affiliation for all authors. Please
check if appropriate. Mee(2017), https://doi.org/10.1016/j.mee.2017.12.010
This is a PDF file of an unedited manuscript that has been accepted for publication. As
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a.
Department of Mechanical Engineering, University of Maryland, College Park
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Fischell Department of Bioengineering, University of Maryland, College Park
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Department of Mechanical Engineering, University of California, Berkeley
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Berkeley Sensor and Actuator Center
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e.
Department of Physics, University of California, Berkeley
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* Ryan D. Sochol, 2147 Glenn L. Martin Hall, University of Maryland, College Park, MD
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Liwei Lin, 5135 Etcheverry Hall, University of California, Berkeley, CA 94720, USA;
lwlin@me.berkeley.edu
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Abstract
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the semiconductor and microelectromechanical systems (MEMS) industries. These
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methodologies have enabled microfluidic platforms to be fabricated with fully-integrated
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microelectronics – a critical requirement for applications such as electrophoresis and
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(e.g., via electrowetting-on-dielectric (EWOD) phenomena), and on-chip electrochemical
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detection. Despite the distinguishing capabilities afforded by conventional
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1. Introduction
significant and wide-ranging advantages for applications in chemistry and biology [1-3],
including rapid thermal and biochemical diffusion times [4], low reagent volumes [5],
laminar flow profiles [6], precision handling of microparticles (e.g., microbeads and living
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cells) [7, 8], and controlled regulation of microenvironmental characteristics [9, 10].
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To benefit from these characteristics, researchers have utilized and/or adapted
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conventional micromachining methods to fabricate fluidic systems at smaller scales [11-
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standard semiconductor materials, including silicon [14] and glass [15, 16]; however,
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disadvantages associated with the use of such materials for microfluidic applications
Bell Labs [20], Duffy et al. introduced a technique for micromolding and bonding the
single layer of PDMS is shown in Figure 1 – left, which consists of five fundamental
steps: (i) photoresist (e.g., SU-8) is spin-coated onto a Si wafer; (ii) microchannel
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designs are photolithographically defined (e.g., using a photomask and UV light); (iii) the
photoresist; (iv) liquid PDMS is poured onto the Si wafer with patterned photoresist,
which serves as a negative master; and (v) after the PDMS is thermally cured, the
molded PDMS is removed from the Si wafer, allowing individual devices to be cut and
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then punched with holes at designated inlet/outlet port locations [22-24]. Following this
micromolding process, the PDMS devices can be bonded to a substrate (e.g., a glass
slide or another PDMS layer) using methods including UV ozone or Oxygen plasma
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comprised of multiple discrete layers that are bonded together – a process termed
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“multilayer soft lithography” [25, 26]. The use of multiple layers allows for each tier to
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serve a distinct functionality. For example, certain layers can operate as relatively rigid
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yield fluidic routing capabilities that mimic those of electronic circuits [27-29]. In addition
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to differences in physical or mechanical functions, each layer can also be designed with
intervening permeable layer that supports biochemical transport for biological studies
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[30-33]. Researchers have also developed methods to create non-planar molds for
applications including microfluidic railing via microchannels with multiple heights [39-42]
components with microfluidic systems. One approach involves the manual insertion of
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conducting wire [47] or other electrode material [48] into microfluidic channels or ports.
Alternatively, the protocols for soft lithography can be adjusted to achieve PDMS
bonding to a substrate with a planar electronics layer, such as a glass slide [49] or PCB
board [50]. Figure 1 illustrates an example protocol for fabricating a microfluidic device
with embedded electrodes. The process for fabricating the metal-patterned glass
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substrate includes five key steps: (i) photoresist is spin-coated onto a glass substrate;
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(ii) electrode designs are photolithographically defined; (iii) a thin layer of a secondary
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metal to support electrode adhesion is deposited (e.g., via physical vapor deposition
(PVD) or electroplating); (iv) a layer of a primary metal electrode is deposited; and then
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(v) the substrate in chemically developed, resulting in liftoff (i.e., removal) of the
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undesired photoresist-metal features (Fig. 1 – right). Thereafter, micromolded PDMS
interface with metal electrodes, pads, and interconnects (Fig. 1 – bottom). To support
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this bonding process and the ultimate sealing of the microchannels, researchers have
layers [51], plasma surface modification [52], dielectric barrier discharge [53], and
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with a conductive nanoparticle filler, such as carbon black [55], silver [55], zinc [56], or
carbon nanotubes [57], prior to thermal curing. This technique allows for the assembly
of vertical sidewall electrodes directly in contact with the microfluidic channel [58] and
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can also be used to place other active polymer composites adjacent to microfluidic
channels [59].
a wide range of on-chip capabilities. In a number of cases, direct fluid contact with the
electrodes is not required, such as for electrode-generated heat sources [60-62] or cell
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manipulation via magnetic fields [63-65]. Similarly, electrically-generated effects can be
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performed with isolated electrodes for applications including fluorescence-activated cell
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sorting [66], electrorheological fluid [67] and valve manipulation [68-70], and droplet
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which individual microfluidic droplets can be manipulated by dielectrically altering their
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surface energy [73] – only partial electrode isolation is required as fluid droplets remain
in direct contact with a common grounding electrode while isolated from control
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electrodes by a layer of dielectric material [74, 75]. In contrast, electrodes are directly
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integrated into microfluidic systems when a direct conducting path into the fluid is
needed, such as for electrophoresis [76], dielectrophoresis [77, 78], fluid manipulation
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via electrokinetic effects [79, 80], and hydrogel [81-83] and cell manipulation [84, 85].
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chemical and biological fields [86]. A critical barrier for those outside of engineering
fields is that gaining access to the necessary equipment for device construction (e.g., in
training and high usage fees [87]. Furthermore, the clean room-based procedures for Si
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wafer processing are typically executed manually, which can be exceedingly cost, time,
and labor-intensive [88]. These issues are exacerbated when fabricating multilayer or
multilevel device designs that require distinct tiers to be manually aligned and/or
assembled – procedures that can diminish the precision and reproducibility associated
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microelectronic advancements on-site can be challenging (especially for those outside
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of engineering fields). Another critical issue is the intrinsic restriction of monolithicity,
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which renders relatively common features of macroscale fluidic components (e.g.,
circular channels with varying diameter, non-planar physical architectures, etc.) difficult
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or impossible to achieve in microscale domains. This monolithicity also constrains the
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assembly and packaging of microfluidic systems to relatively planar geometries [91].
More significantly, planar systems restrict the geometry of applied electromagnetic fields
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[92] as planar electrodes cannot generate parallel electric fields [93] (e.g., a requirement
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for optimal capacitive cell cytometry and droplet detection [94]). Consequently,
limitations could offer significant promise for diverse academic and industrial fields.
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Thus, just within the last few years, research into the potential for 3D printing of
microfluidic devices has already begun to expand the general understanding of the
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[95, 96].
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are used to generate a digital 3D model (e.g., in STL file format), which is then imported
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into computer-aided manufacturing (CAM) software corresponding to a specific 3D
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printer or 3D printing process. Lastly, the resulting 3D printing code (e.g., G-code) is
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electronically imported into the 3D printer to enable autonomous device construction.
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for applications throughout broad academic and industrial fields (e.g., selective laser
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sintering, laminated object manufacturing, and binder jetting), the micro/nanoscale 3D
deposition modeling and direct ink writing, (ii) stereolithography, and (iii) multijet (or
polyjet) modelling.
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Extrusion-Based 3D Printing
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most interest across academic, industrial, and commercial spaces. In 1988, S. Scott
Crump introduced the first extrusion-based 3D printing approach. Stemming from his
experiences making a toy frog (for his daughter) using a hot glue gun loaded with a
mixture of polyethylene and candle wax, S. Scott Crump described and patented an
object is formed using dispensing heads (e.g., nozzles) to directly deposit heated
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(Fig. 2a) [97]. FDM – alternatively referred to as “fused filament fabrication (FFF)” as
polylactic acid (PLA), and polyethylene terephthalate (PET). In the late 1990s,
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Ceserano and Calvert adapted this concept to extrude and deposit pseudoplastic
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materials [98], including ceramics and composites, via a technique termed
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“robocasting”. Further extensions of these methodologies in which materials or “inks”
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3D structures without requiring thermal processing steps (i.e., heating or cooling) are
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characterized as “direct ink writing (DIW)” [99-101].
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Stereolithography
did not file a full patent specification. In 1984, Charles W. Hull filed a patent for a similar
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layer fashion to ultimately fabricate a 3D object comprising cured material (Fig. 2b)
[103]. It should be noted that the initialism “SLA” has since come to be used to describe
the process, rather than the apparatus; however, the initialism “SL” is often used
instead. In developing SLA, Hull also created the widely-used STL file format for 3D
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models, and pioneered the digital slicing and hatching (i.e., infill) approaches that
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adaptations of SLA have included: (i) the use of projection-based photoexposure (e.g.,
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via digital micromirror device (DMD) or digital light processing (DLP) technologies) to
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cure an entire layer at once (in contrast to the point-by-point process inherent to the use
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continuous liquid interface production (CLIP) [105], and (iii) holographic approaches for
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curing entire volumes in a single step [106].
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Multijet Modelling
In the early 1990s, Yamane et al. invented a technique for building 3D structures
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combined with the simultaneous printing of a sacrificial support material [108] and
parallel dispensing strategies [109], became the basis for “Multijet Modelling (MJM)”
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approaches. Referred to as either “Multijet” or “Polyjet” 3D printing, MJM entails the use
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After completion of the 3D printing process, the support material – typically a water-
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McDonald et al. applied an earlier MJM approach, referred to as “solid-object printing”,
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to 3D print various molds for PDMS micromolding (Fig. 3a), enabling microfluidic
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systems with serpentine channels and multilayered vias [112]. Subsequently,
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researchers have extended this work to create molds using SLA [113] and MJM [114].
For example, Hwang et al. created multiple MJM 3D printed molds that can be
assembled to surround liquid-phase PDMS during the curing process, and then
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removed thereafter (relying on the flexibility of PDMS) to create complex PDMS channel
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architectures (Fig. 3b) [117]. Costa et al. used a similar 3D printed template molding
healthy and diseased (narrowed) vascular structures, (ii) using the templates for PDMS
casting, and then (iii) removing the 3D printed templates to leave behind empty
microchannels within the solidified PDMS (Fig. 3x) [119]. Additionally, Glick et al.
decrease the time and labor associated with assembling multilayer microfluidic systems
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with many distinct layers (Fig. 3c) [118]. Compared to the concept of 3D printing an
entire microfluidic system, the use of 3D printing for fabricating molds provides several
advantages: (i) each mold can be used for the fabrication of multiple microfluidic
devices, saving on 3D printing times and costs, and (ii) the process is compatible with
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latter benefit allows for researchers to employ similar micromolding procedures, yet
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achieve geometric characteristics that would be exceedingly difficult to achieve using
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conventional methods. Nonetheless, the molds are still limited in geometric versatility
by the requirement that they must be able to support demolding processes. Thus,
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although 3D printed transfer molding procedures can overcome issues associated with
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clean room-based wafer processing, many of the limitations associated with protocols
efforts have employed FDM to build fluidic systems [124-128], the inherent trade-off
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between feature resolution and fabrication time has limited its efficacy for microfluidics
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materials or “fugitive inks” [101], which can then be casted and subsequently removed.
In particular, the Jennifer Lewis group has pioneered a number of fugitive ink-based
DIW strategies for resolving 3D microfluidic systems. In one of the earliest of these
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ink; (ii) the 3D printed network is then casted with a surrounding liquid resin; (iii) the
resin is solidified via a curing process; and (iv) the fugitive ink is heated to support
hollow, interconnected microfluidic channels (Fig. 4a) [99]. Wu et al. adapted this
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approach by applying an omnidirectional printing technique [129] to print free-floating
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fugitive ink within a reservoir of a photocurable hydrogel (Fig. 4b) [130]. After the
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printing process, the researchers photocured the surrounding hydrogel, and then
evacuated the liquid-phase fugitive ink via vacuum. The resulting system included
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vascular-inspired 3D microchannels within the hydrogel matrix (Fig. 4b) [130]. Using a
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similar approach, Miller et al. 3D printed a 3D carbohydrate glass lattice; however, in
this case, the 3D sacrificial network was encapsulated with living cells and ECM before
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being dissolved in media [131]. Gelber et al. also 3D printed sacrificial structures using
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fluid mixer (Fig. 4c) [132]. Kolesky et al. further extended this approach in a
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combinational method than involved using DIW to bioprint two distinct cell-laden gels
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adjacent to a fugitive ink, which was ultimately removed and then lined with endothelial
demonstrated by Li et al. employing wax jetting for sacrificial material deposition for
microfluidics is the ability to print using multiple filament material extrusion heads [135],
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from a porous material in a single step for the detection of nitrate content in soil [136].
microfluidics with respect to alternative 3D printing approaches and observed that ~600
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~300 μm-wide extrusion nozzle – provided additional surface area for laminar flow
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interfacial contact that expedited diffusive mixing [137]. Thus, FDM can be employed to
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fabricate FDM-printed laminar flow microfluidic mixers; however, the use of FDM-printed
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mixing would not negatively affect the performance of the device [137].
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Microfluidic Systems via Stereolithography
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varied in size, revealing channel resolutions on the order of 300-400 µm and also
presenting methods to improve optical clarity (Fig. 5a) [90]. Concurrently, Shallan et al.
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gradient and microdroplet generators (Fig. 5b) [138]. Bhargava et al. developed a
microfluidic resistors in the form of 750750 µm2 microchannels with varying lengths
(and therefore, resistances) [139]. These elements were utilized for microfluidic
applications including fluidic mixing and droplet generation (Fig. 5c) [139]. Macdonald
et al. revealed that SLA-printed microchannels more reliably and accurately replicated
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as-designed dimensions (~26±20 μm wider) with lower surface roughness than those
The results revealed that SLA offers an effective technology for fabricating microfluidics
devices for applications in which limited laminar flow mixing is required, such as for
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microfluidic device, Urrios et al. demonstrated the use of several types of DLP-based
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SLA to fabricate microfluidic systems using a photocurable low-MW poly(ethylene
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glycol) diacrylate (MW 250) (PEG-DA-250) [140]. In contrast to the aforementioned
systems with static components, Au et al. also presented 3D printed microfluidic valves
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with deformable membranes, which were employed to create a peristaltic pump
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comprised of three valves and a multi-fluid perfusion chamber comprised of four valves
(Fig. 5d) [141]. Other groups have since demonstrated additional SLA-based valving
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printing approach that has been demonstrated, as of the writing of this review, capable
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surface, which can then be sealed to form an enclosed microchannel [145]. Below this
50 μm limit, the pixelated resolution of the UV light source resulted in unintended curing
of resin inside the channels. Because the precise chemical formulation of the SLA resin
has a significant effect on the practical resolution of SLA-printed features, Gong et al.
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absorber molecules as well as lower viscosities than commercial resins [146], which
μm-thick membranes [143]. Recently, the Nordin group further optimized a custom
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knowledge, marks the smallest 3D printed microchannels reported in the literature at
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this time. Additionally, Kotz et al. created an SLA-compatible silica nanocomposite that
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enabled conversion to transparent fused silica glass (via heat treatment) following the
3D printing process, and demonstrated resolutions on the order of tens of microns [148].
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Thus, customization of SLA-compatible photomaterials appears to be a critical area of
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research to further improve the feature resolution and material versatility of SLA-printed
microfluidic systems.
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date, DLW approaches have achieved the highest feature resolutions for 3D printing
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also be a limitation. Specifically, for DLW, the trade-off between voxel size (i.e., the 3D
point of two-photon polymerization) and 3D printing time has typically limited the total
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build volume of 3D printed structures to within the 100 μm3 to 1 mm3 range [155]. Thus,
initial efforts toward using DLW for 3D printed microfluidics involved direct-writing
first loading the photocurable material into microfluidic channels, researchers were able
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diffusion-based mixing dynamics [149] and construct multidirectional fluidic vias [150].
Lamont et al. recently extended this approach to 3D print microfluidic diode components
structures must be self-supporting. For geometries that do not satisfy this condition,
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fully-integrated support structures (e.g., pillar-like ribs) must be added to the design to
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facilitate successful prints [105]. Although such structures can be manually removed
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from macroscale objects following the 3D printing process, doing so for submillimeter-
the most complex physical geometries of any additive manufacturing approach. For
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straight channel geometries, yet demonstrated the potential for integrating non-3D
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printed parts, such as membrane inserts [156]. Lee et al. extended this concept by
components (e.g., channels, mixers, junctions, etc.) could be connected through the use
of non-3D printed rubber O-rings and metal pins to realize functional devices (Fig. 6b)
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single-input-regulated multi-flow controller (Fig. 6c – right) [110]. Sweet et al. later
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extended the use of these components by integrating several 3D printed fluidic circuit
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elements in order to realize finger-powered fluidic pumping and mixing systems [159].
An important benefit of MJM is that devices can be printed not only with a single
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part material and a support material [160], but also with additional part materials (or
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functional gradings of materials) to realize multi-material 3D printed microfluidic systems
[161, 162]. To demonstrate this concept, Keating et al. 3D printed a “Quake Valve” [26]
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with a rigid photoplastic for the overall system, but with a flexible rubber-like material for
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the valving membrane (Fig. 6d) [162]. Recently, Hubbard et al. demonstrated multi-
material microfluidic capacitors, diodes, and transistors, which comprised that comprise
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two distinct materials: (i) a non-compliant photoplastic material for functionally ‘rigid’
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features, and (ii) a flexible photomaterial for deformable diaphragms and sealing O-rings
integration, build volumes, print speeds, and geometric versatility, MJM material
selection remains limited to a relatively small number of proprietary materials [164, 165].
Among the materials that are available, the vast majority are limited in terms of
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biocompatibility, which may impede the adoption of MJM approaches for biological and
leaching of cytotoxic monomers into contacting fluid. For example, conformal PDMS
and polystyrene-based coatings offer one route to enhance endothelial cell adherence
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to inner microchannel surfaces for improved efficiency of cell lysis [166]. Similarly,
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researchers have observed that polyurethane-based scaffold drop-casting coatings can
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improve both substrate cytocompatibility and hydrophilicity for enhanced attachment
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surfaces [167]. In addition, the use of sacrificial support materials results in all internal
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voids (e.g., microchannels) being filled with these materials directly after the 3D printing
component design changes. For example, to remove sacrificial wax support materials
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from device microchannels, Sochol et al. executed a multistep protocol including: (i)
immersing the devices in mineral oil heated to 80 °C; (ii) manually inputting hot mineral
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oil through the microchannels via a syringe; and (iii) inputting pressurized air through
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with additional input/output ports to facilitate this process, such as fluidic diodes that
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required four ports rather than the standard two (Fig. 6c – bottom left) [110]. The use
of water-soluble support materials can alleviate the need for such design changes;
however, it is important to note that the removal process for such materials is diffusion
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physically dislodging it [162] or allowing the material to dissolve over time (often over
multiple days) [137, 163, 168]. The diffusion-limited challenges associated with the
shapes and enclosed structures [169] often guide the design of devices to support
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can accommodate the insertion of a removal tool [156, 162]. Although the addition of
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multiple access ports and external stimuli (e.g., sonication) can accelerate the
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dissolution process [163], the removal time is directly related to the length of internal
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microdevice geometries, such as the DNA-inspired microfluidic system shown in Figure
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6a, would be difficult or unfeasible to achieve due to the challenges associated with the
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mainly stemmed from demonstrating devices with newly manufacturable forms (e.g.,
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predominantly on function – i.e., achieving printable conductive materials with desired
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electrical characteristics [170]. At present, researchers have primarily employed
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extrusion-based 3D printing approaches for electronics applications; however, there
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have been adaptations of such processes to enable new capabilities. In particular, Ahn
substrates (Fig. 7b) [171]. Notably, Zhou et al. further extended these strategies to 3D
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print a silver-nanoparticle ink to create both in-plane and out-of-plane passive radio
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oscillators (Fig. 7c) [172]. The researchers were able to integrate fully printed
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inks during the deposition process to create conductive metallic interconnects and
freestanding spiral architectures (Fig. 7d) [173]. Liu et al. presented an additional
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microelectronics.
One of the key challenges of 3D printing electrically conductive inks is that the
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porosity of fabricated parts may cause electrical shorts due to the spreading of the inks
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on surface layers [175] or between stacked layers [176]. To reduce such issues, one
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approach is to use micromachining techniques to build fine channel features that serve
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manually placed in desired locations (Fig. 8a) [177]. Alternatively, through process
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optimization, conductive inks can be directly printed without the need for guiding
grooves [178-182]. For example, researchers have reported resistivities for silver inks
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deposited silver inks, researchers have demonstrated that local annealing of printed
silver conductive traces yielded a resistivity of 4.3 × 10 −8 Ωm – close to the bulk silver
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porosity [185-188].
technology and its potential uses in the real world become closer to a reality. Gubanova
transistors (ISFETs) for micro volume analysis [189]. Other groups have bypassed
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components, such as capacitors, inductors, and high pass filters as well as copper-
based microwave metamaterials [190, 191]. Additional strategies have enabled more
For example, Muth et al. presented an embedded 3D printing approach that involved
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extruding conductive ink inside of a reservoir of liquid photopolymer to form resistive
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sensing elements for flexible strain sensors [192]. Researchers have also
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demonstrated that the extrusion process itself can be adapted, such that multiple
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Frutiger et al. fabricated capacitive soft strain sensors through an extrusion-based
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multicore-shell printing strategy (Fig. 8b) [193]. Finally, microchannels filled with liquid
metals at room temperature, such as mercury, gallium, and their alloys, also offer a
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potential route to improve the speed and geometric complexity of liquid metal-integrated
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approaches as well. Interest in light driven 3D technologies such as SLA/DLP and DLW
for the creation of conductive structures has increased in recent years due to the
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example, Odent et al. presented elastic and conductive ionic composite hydrogels that
are compatible with SLA processes and demonstrated both elastic deformation and
conductivities up to 2.9 S m−1 (Fig. 8c) [199]. Recently, researchers have adapted
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carbon nanotubes (MWCNTs) [195]. On a much smaller scale, DLW has been used to
composite material [196]. Researchers have also investigated the utilization of SLS for
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conductivity of up to 10 Ωm at just 1 wt% CNTs [202].
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To provide an alternative to DIW of conductive materials, Wu et al. presented an
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approach that entails 3D printing a structure with empty channels, which are
subsequently filled with a conductive liquid metal paste (Fig. 8d) [203]. This strategy
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enabled fabrication of electronic components including resistors, inductors, and
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capacitors, as well as integrated circuits, such as an inductor and capacitor resonant
tank capable of passive wireless sensing functions. Similar to prior works, however, the
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resistivity of the filled liquid metal pasted was measured as 3.6 × 10−6 Ωm due to the
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poor packing density of silver particles inside the channels and inefficient curing
processes [203]. Agarwala et al. adapted this approach to achieve microchannel strain
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technology; (ii) the electronic interconnects are 3D printed via DIW; and (iii) commercial
stages during the 3D printing processes. For example, researchers have demonstrated
3D printed antennas and microwave devices by merging FDM with DIW of conductive
inks [205-207]. Similarly, a number of groups have integrated SLA with DIW (while
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a variety of electronic systems, including motion sensors [208, 209] and timer circuits
(Fig. 8e) [210]. For example, Figure 8f shows a six-sided gaming die consisting of a
problem of such methods, however, is that the photocurable materials currently used for
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SLA processes may be affected by weathering, aging, dimensional changes, and UV
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exposure doses, and thus, could limit the reliability of SLA-DIW-based 3D printed
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electronics [177].
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3D Printing of Semiconductor and Other Electronic Materials
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In addition to polymers and conductors, 3D printed microelectronics can benefit
such as semiconductor, magnetic, and piezoelectric materials; however, there are three
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key issues in producing these materials with high quality via 3D printing processes.
First, most of these materials are made in the form of nanoparticles to be mixed with
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solvents and polymers for desirable printing viscosity and properties with respect to 3D
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structure from the nanoparticles without voids and grain boundaries. Because most
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interconnects. One notable example is a 3D printed quantum dot LED presented by
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Kong et al., which was constructed by interweaving five diff erent materials: (i)
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semiconducting inorganic nanoparticles, (ii) elastomeric matrix, (iii) organic polymers for
charge transport, (iv) metal conductors, and (v) a UV transparent substrate (Fig. 9a)
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[212]. Mannoor et al. demonstrated the ability to create bionic ears by using DIW to 3D
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print a cell-laden hydrogel matrix and an intertwined conducting silver nanoparticle-
based polymer (Fig. 9b) [213]. Sun et al. employed DIW to 3D print Li4Ti5O12 (LTO) and
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LiFePO4 (LFP) in an adjacent architectures to serve as materials for the anode and
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carbon materials was recently reviewed by Fu et al. [215], it is of note that a material of
growing interest in the additive manufacturing field is graphene as well as its oxidized
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and reduced forms graphene oxide (GO) and reduced graphene oxide (rGO) [216-219].
conductivity, and mechanical strength all while being relatively cheap to create and
even biocompatible [218]. Researchers have also demonstrated the ability to 3D print
structures comprising SiO2 [220], ZnO [221], SiC (Fig. 9d) [222], BaTiO3 [223], ZrO2
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[224], and GO (Fig. 9e) [225]. One important caveat, however, is that the efficacy of 3D
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5. Conclusion
Although these efforts have generated considerable interest in academia, industry, and
the general public, in many ways, the overall field remains in its infancy.
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At present, state-of-the-art demonstrations of 3D printing-based microfluidic and
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microelectronic capabilities serve as important first steps toward a longer-term transition
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of emerging technologies from the lab to real-world uses and commercialization. It is
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industrial applications is founded on 3D printing-induced benefits that are unequivocally
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superior to conventional manufacturing methods. In the case that additive
manufacturing protocols continue to suffer from relatively slow fabrication speeds and
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low production volumes, the aforementioned benefits will instead need to stem from the
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printing processes. Thus, it is critical for researchers to focus less on evaluating how
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readily produced using conventional means, and instead, focus more on demonstrating
singular 3D printing approach has thus far exhibited characteristics that would be ideal
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precise resolution for both external and internal features (e.g., for electrodes and
microchannels, respectively), (iii) minimal labor before, during, and after the printing
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process, (iv) high geometric and architectural versatility, (v) a wide selection of printable
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materials, including materials that are biocompatible and conductive materials that
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exhibit low electrical resistivity, (vi) rapid fabrication times, and (vii) low costs.
Unfortunately, recent works have revealed that current 3D printing techniques that are
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beneficial for microfluidics manufacturing suffer from numerous limitations in the context
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of microelectronics fabrication and vice versa.
including FDM and DIW provide significant advantages compared to other additive
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processes for fabricating microelectronic systems [226], yet such approaches are ill-
suited for microfluidics manufacturing [96, 164, 227]. One could employ extrusion-
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material structure, and then execute standard casting and fugitive ink removal protocols
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[99, 130-133] to resolve hollow microchannels that intersect with or run adjacent to the
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for microfluidics manufacturing [95], and current research into custom SLA resin
approaches have not yet been demonstrated for the direct placement and/or integration
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of electrically conductive materials during the 3D printing process. Instead, such
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methods typically require extensive post-process metallization protocols [228-230] that
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continue to be limited by many of the issues associated with conventional
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printed microfluidic systems can be designed to incorporate the manual insertion of non-
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3D printed electronic components [139, 231]. Yet, such protocols are inherently limited
by factors such as labor, precision, and repeatability, and thus, are not ideal for long-
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Rather, we anticipate that the selection and use of a specific fabrication strategy will be
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printing technologies that are ideally suited for both microfluidics and microelectronics
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accelerate the advancement of new generations of 3D printed microfluidic systems with
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full, autonomous microelectronics integration.
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Author Contributions
R.D.S. wrote the abstract, Section 2, and Section 5, illustrated Figures 1 and 2, and
prepared Figures 3-9. R.D.S., C.C.G., E.S., S.-Y.W., and C.Y. wrote Section 1. R.D.S.,
C.C.G., and E.S. wrote Section 3. S.-Y.W., C.Y., and L.L. wrote Section 4. R.D.S.,
C.C.G., E.S., S.-Y.W., C.Y. and L.L. edited the manuscript. R.D.S., E.S. and M.R.
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edited Sections 3, 4 and 5 upon revision.
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Figures
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Figure 3. Examples of using 3D printing to fabricate 3D molds for PDMS curing.
(a) Concept of using a computer-aided design (CAD) file to 3D print a mold that allows
for PDMS replica molding [112]. (b) Illustrations of using multiple discrete 3D printed
molding components (gray) to mold PDMS (blue), after which the 3D printed molds can
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be removed [117]. (c) Concept and results for using double-sided molding procedures
with 3D printed molds to fabricate male-female alignment structures for assembling
complex multilayer microfluidic systems with five distinct layers [118]. (d) Concept and
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results for creating a single-body PDMS device with an enclosed 3D microchannel via
casting PDMS around a solid SLA-printed microchannel template, followed by manual
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distinct fluids followed by droplet generation [139]. (d) A 3D printed microfluidic valve
and a 3D printed multi-fluid perfusion chamber comprising four integrated valves [141].
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