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ReseaRch aRticle
Melt Electrowriting of Isomalt for High-Resolution
Templating of Embedded Microchannels
Ali Nadernezhad, Matthias Ryma, Hatice Genç, Iwona Cicha, Tomasz Jüngst,*
and Jürgen Groll*
DOI: 10.1002/admt.202100221
but also on increased accessibility of low
budget printers.[] Based on availability,
D printing activities have increased in a
broad range of research areas. Particularly,
this led to the acceleration of the develop-
ment of novel materials for AM, and sugar-
based glasses demonstrated their potential
in extrusion-based D printing, mainly as
support material or fugitive inks.[–]
Especially in tissue engineering, rapid
water solubility and ease of removal after
printing rendered sugars into valuable
fugitive materials for D printing as they
help to tackle one of the main challenges
in the field: perfusion and nutrient sup-
port of cell-laden tissue-engineered con-
structs quickly after fabrication. Miller
et al. demonstrated this potential by fab-
ricating delicate microchannels from a
mixture of glucose, sucrose, and dextran solutions as a glass
ink within cell-laden bulk hydrogels using an extrusion-based
approach.[] The dimension of fabricated microchannels
ranged from to μm. Since then, several other studies
attempted to systematically control and enhance the process of
D printing of sugars.[,–]
Nevertheless, tissue engineering was not the only research
field that benefited from AM of fugitive materials. Since the
early s, microchannels created with D printing of fugi-
tive inks gained increasing attention as an alternative to the
traditional soft lithography techniques within the field of
microfluidics. These systems address a long-lasting limita-
tion of soft lithography in expanding the microchannel net-
works from D toward D. The pioneering work by Therriault
etal.[] demonstrated the possibilities of expanding AM toward
microfluidics including D microchannel networks. Although
D printing principles promote exciting and new opportuni-
ties for microfluidics, soft lithography approaches still hold
the advantage over conventional D printing technologies
such as extrusion printing or stereolithography when it comes
to reaching small feature sizes and high surface qualities.[,]
While extrusion-based techniques mostly delivered milliflu-
idic size scales, stereolithography could push the boundaries
below μm. However, the commercially available resins
and printers to achieve such resolutions are very limited.[]
As an alternative to conventional D printing technologies,
methods such as liquid-filled voids for PolyJet printing[]
and Two-Photon direct laser writing polymerization[] allow
the fabrication of feature sizes below μm. However, these
Fabrication of microchannels using 3D printing of sugars as fugitive material
is explored in dierent fields, including microfluidics. However, establishing
reproducible methods for the controlled production of sugar structures
with sub-100 μm dimensions remains a challenge. This study pioneers the
processing of sugars by melt electrowriting (MEW) enabling the fabrication
of structures with so far unprecedented resolution from Isomalt. Based on a
systematic variation of process parameters, fibers with diameters down to
20 μm can be fabricated. The flexibility in the adjustment of fiber diameter by
on-demand alteration of MEW parameters enables generating constructs with
perfusable channels within polydimethylsiloxane molds. These channels have
a diameter that can be adjusted from 30 to 200 μm in a single design. Taken
together, the experiments show that MEW strongly benefits from the thermal
and physical stability of Isomalt, providing a robust platform for the fabrica-
tion of small-diameter embedded microchannel systems.
A. Nadernezhad, M. Ryma, Dr. T. Jüngst, Prof. J. Groll
Department of Functional Materials in Medicine and Dentistry
Institute of Functional Materials and Biofabrication and Bavarian
Polymer Institute
University of Würzburg
Pleicherwall 2, Würzburg 97070, Germany
E-mail: tomasz.juengst@fmz.uni-wuerzburg.de;
juergen.groll@fmz.uni-wuerzburg.de
H. Genç, Prof. I. Cicha
Department of Otorhinolaryngology
Head and Neck Surgery
Section of Experimental Oncology and Nanomedicine (SEON)
Else Kröner-Fresenius-Stiftung-Professorship
Universitätsklinikum Erlangen
Friedrich-Alexander-Universität Erlangen-Nürnberg
Glueckstr. 10a, Erlangen 91054, Germany
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/admt.202100221.
1. Introduction
The impressive development of additive manufacturing (AM) is
not only based on the freedom in design and the field’s pro-
gress from prototyping toward manufacturing technologies,
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approaches are limited due to several technology inherent
challenges, including the very slow nature of the processes
and small build volumes.
These limitations could be overcome by emerging D printing
technologies, such as melt electrowriting (MEW). MEW provides
the opportunity to fabricate delicate microstructures with excel-
lent reproducibility and precision.[] It is an AM process based
on the application and manipulation of electrohydrodynamic
forces to guide and deposit micrometer-sized fibers ranging
between .[] and μm[] in well-defined patterns. A com-
puter-controlled movement of the collector delivers direct control
over the deposited pattern. A significant aspect of MEW relevant
for the applications involving embedded microchannels relies on
the possibility of adjusting process parameters on-the-fly. This
makes MEW a one-step fabrication process to realize on-demand
feature sizes with great variety. Hrynevich etal. showed that by
changing a single MEW factor in a controlled way, the fiber diam-
eter in a simple mesh structure could be altered by one order
of magnitude.[] Despite these benefits, MEW is a demanding
process concerning the choice of compatible materials. In addi-
tion to the high sensitivity of the direct writing process on mate-
rial changes, the high resolution realized by the small fiber
diameters implies extended fabrication times. In particular, the
need for materials with low thermal degradation has limited
the availability of materials and rendered poly(ε-caprolactone)
the gold-standard material for MEW.[] Despite that limitations,
MEW has already proved its feasibility to generate micrometer-
sized perfusable channels for microfluidic applications based on
the fugitive approach.[,] A limitation yet to be addressed for
these approaches is the harsh conditions during the removal
of the poly(ε-caprolactone) fibers from the microfluidic devices.
Taken together, MEW would benefit from thermally stable,
water-soluble materials to advance in the area of microfluidics as
those used for conventional extrusion D printing.
Although sugar-based inks demonstrated their potential for
extrusion D printing and might be potential candidates that
help overcome the MEW limitations, some technical aspects
should be noted. Incorporating water in formulations of sugar
glass mixtures can significantly impact the crystallization, vis-
cosity, and degradation kinetics of the sugar glass inks.[] More-
over, the high temperature of the D printing process can result
in caramelization of the sugars, especially during the extended
holding time of the sugar glasses at high temperature during
extrusion, which can alter the degree of polymerization.[] This
would consequently alter the ink’s rheological and mechanical
properties during and after the extrusion, resulting in diculties
in reproducibility and control of the fabrication process, espe-
cially if a process sensitive to small changes in material’s proper-
ties such as MEW is considered. A potential sugar candidate to
overcome these limitations is Isomalt. Isomalt is a sugar alcohol
derived from sucrose in a two-step process and is an approxi-
mately equimolar mixture of α--glucopyranosyl---mannitol
(GPM) and α--glucopyranosyl---sorbitol (GPS). Crystalline
Isomalt melts around – °C, which yields a glassy state
after cooling with a glass transition around °C.[] The melting
temperature of Isomalt is significantly lower than that of the two
isomers, which is attributed to the formation of a simple eutectic
between two sugar alcohols.[] An interesting property of Iso-
malt is that, unlike the other sugar alcohols, Isomalt does not
degrade upon melting.[] This behavior could play a significant
role in considering Isomalt for processing methods that involve
heating at elevated temperatures during processing, such as
MEW. Moreover, Isomalt is a readily available material at low
cost, with minimal variations in properties due to regulatory
requirements for a sugar substitute in the food industry.
Based on these considerations, we hypothesize that Isomalt
is a potential candidate material that enables the fabrication of
fugitive fibers within a wide range of dimensions in a reproduc-
ible way via MEW. To prove this hypothesis, we show that by sys-
tematic variation, precise adjustment, and control of the process
parameters, water-soluble Isomalt fibers in the range from to
μm diameter can be generated with MEW for the first time.
In addition to an analysis of process-related thermal properties
of Isomalt and presenting an operational window based on fiber
diameter versus MEW process parameters, a preliminary proof-
of-concept study demonstrates the flexibility of MEW in combi-
nation with Isomalt for the production of perfusable channels
potentially relevant for microfluidic applications. The channels
generated within PDMS after a water-based dissolution step of
the fibers had adjustable shapes and varying diameters.
2. Results and Discussion
MEW involves stretching and drawing a very thin fiber driven
by the balance between mechanical, gravitational, and electrical
forces opposing the viscosity and surface tension of molten
material at the nozzle tip.[] Due to the extremely hygroscopic
nature of Isomalt, the stability and continuity of the formed jet
and, more importantly, the fidelity of deposited Isomalt micro-
fibers would significantly be influenced by environmental
conditions. Our preliminary experiments (data not shown)
confirmed that at normal laboratory environmental conditions,
the extreme hygroscopic nature of Isomalt results in conden-
sation and local dissolution of micrometer-sized Isomalt fibers
caused by environmental humidity, and consequently loss of
shape and integrity. This eect was more pronounced when the
fiber dimensions reached below μm. To enable systematic
control over experimental and environmental conditions, all the
experiments were conducted in an environmentally monitored
chamber (Scheme 1; Figure S, Supporting Information). By
stabilizing the environmental conditions, the reproducibility of
the MEW process was ensured, and at the same time, the influ-
ence of day-to-day variations of environmental temperature and
humidity on the process were minimized.
2.1. Characterization of the Isomalt Glass
As thermal properties of any candidate material for MEW
play a significant role in the feasibility of the process, ther-
mally stable materials with suciently high viscosity are a
reasonable choice. Figure 1A,B shows the DSC and TG ther-
mograms of Isomalt. Within the early stage of heating up to
°C, only .% of mass loss was observed, which can be
attributed to dehydration (Figure A). The onset of thermal
degradation followed by a massive mass loss was found to
be at . °C. Overall, Isomalt showed excellent thermal
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stability at temperatures below °C, which contrasts with
the other sugar candidate materials such as sucrose, fructose,
and glucose. Although these sugars are water-soluble and sti,
sucrose-, glucose-, and fructose-based glasses tend to easily oxi-
dize by increasing temperature.[]
The phase transition during heating and cooling of Isomalt
was characterized by dierential scanning calorimetry (DSC),
and the results are shown in FigureB. Isomalt is a hygroscopic
sugar alcohol that undergoes crystallization upon hydration
during storage. The first heating cycle in DSC showed two
peaks, one related to dehydration with the peak at . °C, and
the second peak was due to the melting of the crystal domains.
However, the first cooling cycle did not show any crystallization
upon cooling, and only a glassy phase until reaching the glass
transition was observed. On the other hand, the second heating
cycle showed only a glass transition at Tg= . °C, and further
heating did not induce any phase transitions. Sugars can slowly
undergo crystallization by being kept above their glass transition
Scheme 1. A) Schematics of the MEW device including 1) inlet pressurized nitrogen gas, 2) resistive heating element containing two separate elements
for the cartridge and nozzle sections, 3) high-voltage source, 4) collector plate capable of moving in three directions, and 5) environmental chamber
controller to set the relative humidity (RH) and temperature of the chamber. B) Drawing to show the configuration of the nozzle and the formed jet
due to pulling force of electrical field during fiber deposition.
Figure 1. Thermal and rheological analysis of Isomalt to investigate compatibility with the MEW process. A) TG profile during heating from 20 to
900 °C. B) DSC profile of first and second heating-cooling cycles showing the glassy state of Isomalt at high temperature. C) DSC profile of Isomalt
during cyclic heating-cooling of glass after removing the thermal history. The applied thermal regime mimics the thermal protocol used in MEW.
D) Rheological characterization of Isomalt showing a significant increase in complex viscosity over the experimental frequency range by decreasing the
temperature of the glass from 130 to 65 °C in a 1 °C per step manner.
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for a long time. Moreover, shear is known to accelerate the crys-
tallization of sugars at a glassy state.[] This can cause clog-
ging of the nozzle during the extrusion of glass from a fine
nozzle. Unlike the other heat resistive sugars such as lactitol
and maltitol, Isomalt is not prone to crystallization even when
kept at high temperatures for extended time periods like those
expected during fabrication since the crystallization kinetics of
Isomalt depends on the hydration degree. Crystallization of Iso-
malt occurs by the formation of dihydrates, which can be decel-
erated or almost prevented through dehydration.[] Consid-
ering the mechanism and kinetics of crystallization in Isomalt,
a single melting step followed by cooling above the glass transi-
tion temperature will result in the formation of a stable glassy
state, as long as the environmental humidity is monitored and
controlled. The thermal stability and consistency in structural
properties of Isomalt is a determining factor for the application
of this material in processes such as MEW, which rely on con-
tinuous deposition of fibers from a material reservoir kept at
elevated temperatures. Since the dynamics of processes such as
MEW heavily rely on the establishment of a balance between
several opposing factors, consistency and stability in the phys-
ical properties of the material are of great importance.[] The
phenomena such as degradation, polymerization, and crystalli-
zation could significantly alter the physical properties of molten
or glassy sugars. A cyclic DSC study revealed that after removal
of thermal history, Isomalt glass shows a consistent thermal
profile during a cyclic heating-cooling regime (FigureC). This
would further confirm that by following a predefined protocol
of removing the thermal history, the physical properties of Iso-
malt would remain unchanged during MEW processing. In this
way, Isomalt oers a stable glassy state at high temperatures in
controlled environmental conditions, hence contributing to the
stability of the delicate balance governing successful jet forma-
tion in MEW.
We hypothesized that by maintaining a glassy state, Isomalt
at high temperatures could be extruded or dispensed through
a fine nozzle as long as the glass’s viscoelastic properties allow
the formation of a continuous jet. Rheological characterizations
showed that the complex viscosity of Isomalt glass increased
about five orders of magnitude by decreasing temperature from
to °C (FigureD). At high temperatures, Isomalt glass
could be easily deformed, and the low viscosity would result
in the formation of droplets instead of continuous flow. How-
ever, decreasing temperature resulted in a significant increase
in viscosity of the glass, followed by exhibiting shear thinning
behavior. At °C, the carbohydrate glass showed excessive
shear thinning behavior in a wide range of frequencies, with
almost one order of magnitude decrease in the value of com-
plex viscosity by sweeping from low to high frequencies.
Considering the thermal and rheological characterization of
Isomalt, it was envisioned that, by maintaining the glassy state
at a suitable temperature, a continuous flow of material for the
jet formation during MEW could be achieved. Initial screening
experiments (data not shown) revealed that lowering the set
temperature in the two-component heating unit to °C (car-
tridge zone) and °C (nozzle zone) enabled a continuous flow
of glass with proper flexibility of the fiber during the deposi-
tion. In this way, the bulk of glass within the syringe cartridge
had enough viscosity to tolerate above-atmospheric pressures,
while the extruded glass showed pronounced shear-thinning
behavior enabling the drawing of very fine microfibers from the
nozzle with the aid of the applied electrical field.
2.2. Melt Electrowriting of Isomalt
A series of experiments were designed to investigate the pro-
cessability of Isomalt glass with MEW. Three main param-
eters of the MEW process were selected and systematically
changed between five equidistant levels to obtain and assess an
operational window for the production of fibers with dierent
diameters. Table 1 shows the configuration of constants and
the investigated parameters and the corresponding values for
each level. The investigated parameter space did not include
dierent temperatures, since our preliminary results (data
not shown) indicated that alteration of the temperature of the
nozzle results in a significant shift in parameter space, mainly
due to significant change in viscoelasticity of Isomalt glass. For
this reason, the influence of temperature in resulting MEW
fiber diameter was not considered.
Initially, the critical translation speed (CTS) for the produc-
tion of straight fibers in each experimental set was determined.
Determination of CTS, as the transition point between coiled to
straight fiber deposition, is crucial in further analysis of print-
ability.[] Figure 2A shows the influence of dierent process
parameters on the CTS, accompanied by an exemplary image
of the transition between two deposition behaviors at CTS.
An increase in CTS value usually indicates the formation of a
faster jet during the MEW process. This phenomenon could be
explained by considering the correlation between the pulling
force induced by the applied electrical field and the mass flow
through the nozzle.[] Lower pressure resulted in less mass
flow from the nozzle in a constant electrical field intensity,
which resulted in whipping and deviation of the formed thin
fibers from the designed path.[] Similarly, at a constant pres-
sure, increasing the applied electrical field resulted in more
jet instability. To compensate for the induced whipping eect,
the collector speed should be increased continuously to enable
straight fiber deposition. Decreasing the distance between the
nozzle and the collector also resulted in the formation of a
faster jet. A faster jet could result from the increased electrical
force exerted on the glassy jet, even though the same nominal
value of the electrical field was applied to both poles.
After determining CTS for forming a stable jet for each
experimental condition, the next step was to investigate the
influence of these sets of parameters on the deposited glass
fibers’ diameter. FigureB shows the measured values of depos-
ited fibers by varying one process parameter at a time. The col-
lector speed in these experiments was set to be % above the
CTS value for respective sets, ensuring the observed changes in
Table 1. MEW parameters and the corresponding values.
Parameter Parameter range/step size Center value
Applied pressure [bar] 1.0–3.0/0.5 2.0
Applied voltage [kV] 4.0–6.0/0.5 5.0
Tip-to-collector distance [mm] 1.5–3.5/0.5 2.5
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fiber diameters are not due to stretching of glassy jet because of
mismatch between mass flow and mechanical pulling forces.
In all three categories of parameters, changing the corre-
sponding variable’s value resulted in a significant fiber diam-
eter change (p< .). Despite the almost uniform change in
each experimental category’s diameter values, the occurrence
of outliers at extreme values of each parametric range resulted
in the deviation of measured average values from the expected
trends. Increasing the applied pressure to . bars resulted in
an imbalance of mass flow and electrohydrodynamic (EHD)
forces applied to the glassy material at the nozzle tip and
resulted in a phenomenon termed “pulsing” of the electrified
molten jet.[] At these conditions, the diameter of the fiber
changes periodically. During the increase of pressure from .
to . bars, the experimental observations showed that the jet’s
stability was significantly influenced by increasing the mass
flow. However, this impact did not result in an evident periodic
change in diameter, as was expected during fiber pulsing. We
speculate that the jet’s overall stability could be compromised
by increasing the pressure above . bars, but the extent of
this eect is proportionally dependent on the applied pressure.
Noteworthy, the large variance of the fiber diameter observed
by increasing the applied voltage to .kV was not mainly due
to the pulsing eect. We speculate that the observed behavior
could be attributed to the speed of the glassy jet descending
upon the collector surface. Given a constant travel distance
from the nozzle to the collector, a faster jet would result in a
shorter travel time, leading to the deposition of softer glassy
fiber with higher temperature. This might cause the local
spreading and deformation of the fibers with broader statistical
deviations. It should be noted that experimental and computa-
tional data showed that in addition to natural convection and
radiation, EHD eect could enhance the heat transfer during
the landing of the molten jet.[] The possible counter-influence
of EHD heat transfer enhancement on the cooling of glassy Iso-
malt jet could compensate for the shorter cooling period during
the landing of high-speed jet, but confirmation of this hypoth-
esis would need detailed characterizations which are not in the
scope of this study.
A significant variation in fiber diameter at large tip-to-
collector distances was observed. This eect can be attributed
to the plasticity of the jet, where the larger distance at constant
applied voltage leads to weaker electrohydrodynamic forces
and thus a slower landing of the jet. The slower travel speed
Figure 2. Influence of MEW parameters on CTS value and the resulting fiber diameter. A) Variation of CTS based on dierent parameter combinations
in three categories of parameters. An exemplary image of MEW Isomalt glass fibers showing the transition of deposited fibers from coiled to straight
by reaching CTS. B) Influence of three MEW parameters on Isomalt glass fiber diameter. The deposition velocity was set to 10% higher than the cor-
responding CTS value for the respective combination of process parameters. An exemplary image shows the morphology and quality of produced
Isomalt fibers deposited in predefined patterns.
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promotes lower jet temperature upon landing, causing artifacts
in deposited fibers due to mechanical forces induced by the
lack of plasticity.
Despite the challenges in stabilizing fibers at the extremes
of the investigated experimental window, it was observed that
by adjusting easy to control parameters, successful deposi-
tion of Isomalt microfibers with reasonable control over the
dimension could be achieved. In contrast to conventional
extrusion D printing, the combined application of electrical
and mechanical forces to draw a fine fiber in MEW provides
the technical advantage of working with materials with higher
inherent viscosity. On one hand, this implies the possibility of
lower process temperatures, which is in favor of avoiding the
thermally induced deterioration of material’s properties. On the
other hand, the higher viscosity of the melt or glassy material
could potentially enhance the resolution and the stability of the
drawn fibers at the same time. The excellent processability of
Isomalt by MEW could be correlated with the ease of drawing
a thin glassy jet with enough plasticity and viscosity to yield
stable fibers with controllable dimensions.
2.3. High-Resolution Templating of Microchannels
As mentioned in the introduction, MEW is a powerful method
for the fabrication of fibrous constructs with well-ordered
microstructure.[] A significant aspect of this technology is the
potential to alter the process parameters on-the-fly, meaning
that deployment of continuous and on-demand features of the
design is possible. Previous studies using poly(ε-caprolactone),
the “gold standard” material in MEW, showed that by merely
changing the collector’s speed, a wide range of fiber diam-
eters between and μm within the same construct could
be achieved.[] It has also been shown that a systematic vari-
ation of several process parameters enables optimization and
parametric prediction of the MEW process.[] With such flex-
ibility in controlling the dimensional features using MEW, fab-
rication of templating structures from Isomalt could provide
the opportunity to create microchannels within a substrate with
multiple scales of hierarchy. It should be noted that the experi-
mental window for the fabrication of Isomalt fibers by MEW is
not limited to the investigated sets of parameters reported so
far in this study and their corresponding ranges. Practically, as
long as the balance between mass flow and the electrohydrody-
namic forces could be maintained, a stable jet formation would
be expected.[]
The Isomalt fibers can be quickly and selectively dissolved by
exposure to humidity, or generally an aqueous media. Recent
reports on D printing of sugars showed that by embedding
such structures in a matrix of choice, it was possible to gen-
erate channels for dierent application fields ranging from
microfluidics to biofabrication. Selective casting and removal
of sacrificial geometries is a well-established method for the
generation of hollow structures, including microchannels; how-
ever, increasing the design’s intricacy would practically limit
its applicability.[] In this respect, a fugitive structure made of
a water-soluble sugar such as Isomalt with dierent dimen-
sions and structural complexity levels would significantly
extend the manufacturing possibilities. In order to facilitate
the embedment of sacrificial fibers, the MEW of Isomalt was
directly performed on PDMS substrates. Although the electrical
conductivity of PDMS is less than glass substrate, glass is more
prone to undergo polarization in a constant electrical field due
to the higher relative permittivity. This combination resulted in
almost similar behavior of two substrates, and the jet formation
was not significantly impacted. Modeling the electric field dis-
tribution and the applied electric potential on each substrate’s
surface showed consistency in the electric field’s distribution
and intensity during applying dierent electrical potentials to
the nozzle (Figures S and S, Supporting Information). How-
ever, suppose a thorough characterization of the MEW process
using a PDMS substrate is desired. In that case, the inter-
ested reader is encouraged to follow the similar methodology
described in the previous section to derive a more detailed cor-
relation between fiber diameter and MEW parameters.
To investigate the suitability of Isomalt glass fibers produced
by MEW for the fabrication of microchannels, intricate designs
based on continuous fiber deposition with multiple levels of
diameter change were evaluated and transferred to a proof-of-
concept study. Figure 3 shows the region-based alteration of
MEW parameters to fabricate a continuous path with diameters
varying between and μm. The first region of the micro-
channel design mimics the conventional inertial focusing/
mixing design in conventional microfluidics. The curvature of
the channel in this region led to a sequential change in fiber
diameter, which might be of interest in specific applications
such as continuous inertial focusing of flow or microparticles[]
(Video S, Supporting Information). In the study presented
here, that region was added to demonstrate the flexibility of
MEW in adjusting and altering the geometry of the deposition
pattern. It is worth mentioning that the implementation of this
region of the design by MEW was the most demanding por-
tion of the process. The deposition of thick fibers in this region
required pushing the MEW process to the limits that were not
accessible in the previous section’s parameter space. This was
mainly due to the restrictions in translation speed and applied
voltage imposed by the requirements in Section .. Hence,
a change in the parameter space was required. Further on, a
region with the gradual reduction in diameter connected to
a long microchannel with a fixed value of diameter was pro-
duced (Video S, Supporting Information). A controlled change
in the diameter of microchannels provides the possibility to
achieve adjustable flow rates within the design, even with a
constant inlet pressure or flow rate. This feature might be espe-
cially appealing for applications involving the analysis of flow
behavior in microfluidics or tissue engineering. The significant
technological aspect in the fabrication of such structures lies
in the correlations between the actual diameter of the depos-
ited glassy fibers and the on-demand and automated change of
MEW parameters implemented within the G-code path plans.
By removing the MEW Isomalt fibers from the PDMS matrix
using a simple immersion in a water bath, a hollow and per-
fusable continuous microchannel platform with accurately
designed dimensions was produced.
The current literature on templating microchannels using
D printing of sugar glasses reveals the technological limita-
tions of reaching sub- μm dimensions.[–,,] Our demon-
strated proof-of-concept study shows that by applying MEW,
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the resolution can be significantly advanced down to channel
diameters of μm. Beyond that, it additionally opens the pos-
sibility to fabricate geometries with a wide range of dimensions
with size scales ranging from the domain of conventional D
printing technologies down to the limits of lithography-based
techniques in a one-step process.
3. Conclusions
We demonstrate the applicability of MEW for the well-
controlled production of microfibers from Isomalt. The
results show that by precise control over the MEW parame-
ters, Isomalt glass microfibers with a wide range of diameters
down to μm can be fabricated. The water solubility of Iso-
malt provides an easy-to-implement method for the removal
of embedded fibers in the final structure, resulting in the for-
mation of perfusable microchannels with on-demand control
of the diameter. The flexibility of this process was shown in
a proof-of-concept design of microchannels with controlled
alteration of fiber diameter between and μm in a one-
step fabrication process. This one-step fabrication procedure
represents a technological step ahead, which addresses the
current limitations in the production of templating struc-
tures from fugitive sugar glasses in application areas such as
microfluidics.
4. Experimental Section
Materials: Isomalt (E953) was supplied from a local vendor (TeKa
Food GmbH, Germany) and used without further purification. Silicon
elastomer kit (Sylgard 184) was purchased from Dow Corning. Aqueous
dispersion of 10 μm polystyrene (PS) microbeads was purchased from
Sigma-Aldrich.
Thermal Analysis: Netzsch DSC204 F1 Phoenix dierential scanning
calorimetry (DSC) was used to characterize the thermal properties of
Isomalt. The heating/cooling rate was set to 10 K min−1. Thermal gravimetric
analysis of Isomalt was performed using Netzsch TG 209 F1 Iris within the
temperature range of 20–900 °C with a heating rate of 10 K min−1.
Rheology: Viscoelastic properties of Isomalt at high temperature was
characterized through sequential frequency sweeps during 1 °C stepwise
cooling from 130 to 65 °C. For this purpose, Anton Paar MCR702
rheometer equipped with 25 mm parallel plate geometry was used.
Frequency sweeps between 1 and 100rad s−1 were performed at each
temperature interval while the applied strain was kept constant at 0.1%.
Imaging: Optical imaging of the melt electrowritten Isomalt fibers
was performed using Discovery V20 stereomicroscope (Carl Zeiss
Microscopy GmbH, Germany). Perfusion of microparticles through the
embedded channels was photographed with Zeiss Axio Vert. A1 (Carl
Zeiss Microscopy GmbH, Germany) inverted microscope equipped with
a high-speed camera (Phantom High Speed, Vision Research, USA).
Melt Electrowriting: The MEW device (Scheme 1) was enclosed
in a closed chamber connected to an environmental controller for
temperature and humidity (ACS Discovery, ATT Umweltsimulation
GmbH, Germany). The chamber’s relative humidity and temperature were
set to 18 ± 1% and 39 ± 1 °C, respectively. The MEW device included a
heated reservoir mounted on a computer-controlled 3-axis platform.
Figure 3. An example of an intricate design of microchannels produced from Isomalt glass fibers in a single run, through controlled on-the-fly adjust-
ment of MEW parameters. Regions 1 and 3 of the design mimicked the conventional designs of microchannels in microfluidics with a transition Region
2 connecting both designs in a controlled and stable way. Fiber diameter was decreased from 200μm in Region 1 to 30μm in Region 3, with three
steps of subtransitions within Region 2 using four easy-to-control parameters. The collector speed in Region 2 was increased exponentially through a
ten-step discrete incremental loop. The hollow channels embedded in PDMS could be further perfused with polystyrene (PS) microparticles (magnified
subpanels). The perfusion of microchannels and the design induced flow velocities are available in Video S1 and S2 in the Supporting Information.
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Pressurized nitrogen gas was connected to the melt reservoir through an
automated valve. The high-temperature reservoir included two separate
sections for heating the syringe-based cartridge and the nozzle with
dedicated controllers. The nozzle and the build plate were connected to
a computer-controlled high-voltage source (HCP 14-20000, FuG Elektronik
GmbH, Germany). A central control unit (Bosch Rexroth AG, Germany)
was used to drive the three-axis platform and trigger the corresponding
signals for temperature, applied pressure, and applied electrical field
controllers as integrated functions during the execution of the G-code
path planning. For MEW of carbohydrate glass, glass syringes filled
with the granules were placed in the heating unit preheated at 170 °C
to ensure removing all the thermal history by complete melting. After
30min, the heating unit’s temperature was gradually decreased to the set
process temperature and was kept for 30min before printing to ensure a
thermal equilibrium is reached. The Isomalt fibers were printed on 1.1mm
thick glass slides (VWR, Germany), placed on the stainless-steel collector.
MEW Process Parameters: The selected MEW process parameters
were systematically changed between five equidistant levels according
to Table 1. Only one parameter was changed at a time, and the other
variables were set as the center values of corresponding ranges. The
critical translation speed (CTS) was first identified for each set of
parameters. To ensure deposition of straight fibers and minimize the
change in fiber diameter due to stretching of the fibers, the collector
velocity for each series of experiments was set to 10% higher than the
corresponding CTS value for the respective combination of process
parameters. The measured fiber diameters (n= 300) from microscopy
images were evaluated with a one-way analysis of variance (ANOVA),
and the dierences with p-values lower than 0.05 (p< 0.05) were
considered as statistically significant.
Numerical Modeling: The impact of dierent substrates on the MEW
process was modeled numerically in Comsol multiphysics using the
AC/DC module (Comsol Inc., USA). The electric field distribution in
stationary DC field was done by solving the Maxwell equation with the
boundary conditions used based on the experimental parameters. The
values of the electrical conductivity and permittivity of glass and PDMS
were obtained from the Comsol library and literature.[29] The influence
of the substrate on electrical field distribution with dierent applied
electrical potentials (4.0–6.0kV with 500V increments) was evaluated.
Fabrication of Templated Microchannels: Silicon elastomer resin was used
to fabricate Polydimethylsiloxane (PDMS) slabs with a thickness of 1mm.
The resin was cast in an aluminum mold and cured at 150 °C for 9min.
The cured slabs were used as substrates during MEW. The Isomalt fibers
were directly deposited onto the PDMS surface. During printing, process
parameters were extensively altered to precisely control the diameter of
deposited fibers based on the design. After printing, the PDMS substrate
and the deposited fibers were gently moved to an aluminum mold, and
freshly prepared silicon elastomer resin was slowly poured over the printed
fibers. The embedded fibers were left at room temperature for 48 h to cure
the resin completely. The inlet and outlet points of the resultant structure
were generated using a 0.9 mm biopsy punch. The embedded fibers
were soaked in Milli-Q water and kept at 60 °C for 24 h for the complete
dissolution of Isomalt fibers. The PDMS slab with embedded channels
was attached to a plasma-activated microscopy glass slide. The fabricated
channels’ patency was assessed by perfusion of 0.1 wt% dispersion of
10μm PS microbeads in 35% PEG 400 solution in Milli-Q water.
Supporting Information
Supporting Information is available from the Wiley Online Library or
from the author.
Acknowledgements
This work was funded by the Deutsche Forschungsgemeinschaft (DFG,
German Research Foundation) with project number 326998133-TRR
225 (subproject B02) and the German Federal Ministry of Education and
Research (BMBF) project SOP-Bioprint with contract number 13XP5071A.
The authors thank the Industrielle Gemeinschaftsforschung IFG and the
Arbeitsgemeinschaft industrieller Forschungsvereinigungen AIF (IGF-
Vorhaben No. 19054 N) for the support that enabled to set up the MEW
printer used for the study and the European Union for support on printing
strategies (European Fund for Regional Development - EFRE Bayern,
Bio3D-Druck project 20-3400-2-10). Tomasz Jüngst would also like to
thank the European Union for funding by the European Union’s Horizon
2020 research and innovation program under grant agreement 874827. All
authors thank Christoph Böhm and Juliane C. Kade for their assistance
in TG and DSC data acquisition. The assistance and expertise of Andrei
Hrynevich and Gernot Hochleitner in designing and setting up the MEW
printer are highly appreciated.
Open access funding enabled and organized by Projekt DEAL.
Conflict of Interest
The authors declare no conflict of interest.
Data Availability Statement
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
Keywords
embedded templating, melt electrowriting, microfibers, microfluidics,
sacrificial printing, sugar glass printing
Received: February 23, 2021
Revised: April 19, 2021
Published online: June 20, 2021
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