The International Journal of Advanced Manufacturing Technology (2024) 132:533–551

https://doi.org/10.1007/s00170-024-13344-x

ORIGINAL ARTICLE

Design, fabrication, and penetration assessment of polymeric hollow

microneedles with different geometries
Pol Vanwersch1,2 · Tim Evens2 · Albert Van Bael2 · Sylvie Castagne1

Received: 13 September 2023 / Accepted: 22 February 2024 / Published online: 12 March 2024
© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2024

Abstract
Hollow microneedles (HMNs) are minimally invasive needle-like microfeatures usually arranged in arrays designed for drug
delivery and body fluid collection in a painless manner. In a recent work, we demonstrated a novel methodology to mass
produce hollow polymer microneedles at a low cost. This methodology combines ultrashort pulse laser ablation to create
inverse needle shapes in moulds and replication through polymer injection moulding. For a HMN to be functional, it should
effectively pierce the skin at a low force and enable fluidic passage through the skin without leakage. This study investigates
the impact of different laser scanning strategies on the cavity morphology and analyses how the various geometrical charac-
teristics of the needle influence the penetration efficacy. To assess the penetration behaviour of the replicated HMNs, a com-
bination of agarose gel and Parafilm® is employed as an in vitro testing platform. Furthermore, a correlation between HMN
geometry, penetration performance, and modification of polymer material and holding pressure during injection moulding
is established. The results indicate that a certain needle length is essential for effective penetration. Moreover, minimising
the tip area, a factor significantly affecting penetration force, can be achieved by increasing the eccentricity of the scan-free
area and expanding the scanning diameter. However, it is important to consider other functional needle features such as the
ridge height or full lumen, which come at a cost to the tip sharpness. This work highlights the multiple interactions between
the scanning strategy, the injection moulding process parameters, the needle geometry, and the penetration force. This study
provides insights into optimization of the HMN design and the fabrication for enhanced penetration efficacy of functional
injection-moulded polymeric HMNs.

Keywords Hollow microneedles · Injection moulding · Ultrashort pulse laser ablation · Penetration force · Artificial skin

1 Introduction techniques. For example, selective etching can be used to

Hollow microneedles (HMNs) are minimally invasive nee-
dle-like microfeatures usually arranged in arrays designed
to pierce the external skin layer, for the delivery of drugs
to the body or the collection of body fluid. They are gain-
ing popularity as, among else, vaccine delivery systems [1]
and interstitial fluid extractors [2]. Compared to traditional
(hypodermic) needles, HMNs can be used for self-medi-
cation and cause no pain thanks to their short length [3].
HMNs can be manufactured using a variety of materials and
* Pol Vanwersch
pol.vanwersch@kuleuven.be
1
Department of Mechanical Engineering and Flanders
Make@KU Leuven ‑ M&A, KU Leuven, Leuven, Belgium
2
Department of Materials Engineering, Diepenbeek Campus,
KU Leuven, Diepenbeek, Belgium
create silicon HMNs [4], while micromilling can be used
to produce stainless steel HMNs [5]. Ceramic HMNs can
also be made using ceramic casting [6]. While enabling a
wide variety of needle designs, these flexible manufactur-
ing techniques are not suitable for mass manufacturing. In
a recent work, we demonstrated a methodology for mass
manufacturing polymeric HMNs using injection moulding
with laser-ablated moulds [7]. In this process, the inverse
of the needle shape is created in the mould with an ultra-
short pulse laser using a cross-hatching scanning strategy,
and the replication of the needles is achieved with a con-
ventional injection moulding machine. For these HMNs to
be effective, it is important that they penetrate easily into
the patient’s skin. HMNs can be found in a wide variety of
shapes and sizes, but previous studies suggest that the tip
area and wall angle are the most influential geometrical
parameters for the penetration force in skin [8]. This can be

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tested with artificial or ex vivo skin models, or in a digital
environment (i.e. in silico). Penetration tests on artificial
skin models are typically performed with multiple layers of
Parafilm® [9, 10], or with a juxtaposition of polyurethane
foil and agarose gel [11]. In vitro tests are highly repeat-
able and controllable but can lead to a different penetration
behaviour than real-life applications. On the other hand,
ex vivo models, which can range from porcine skin [12] to
rat skin with a supporting PDMS layer [13], can have low
repeatability because of the high variability in skin tissues,
but they can be useful as a final validation tool for penetra-
tion. The human skin is the most suitable for penetration
testing. However, its use is subject to strict regulatory rules
[14]. In silico models are easily tuneable but are highly
dependent on the boundary conditions and can require high
computational power [15]. From the available literature, it
is clear that the shape of a HMN has a large influence on its
piercing behaviour and that the morphology of injection-
moulded HMNs is impacted by both laser scanning strategy
and injection moulding process parameters. However, to
the best of the authors’ knowledge, there exists no report of
functional hollow microneedle geometry that can be fab-
ricated with injection moulding and laser-ablated moulds.
In this work, different HMNs are fabricated with injection
moulding and their penetration behaviour is analysed using
a combination of agarose gel and Parafilm®. Firstly, the
influence of the laser scanning strategy on the cavity mor-
phology is studied. Secondly, the influence of the polymeric
needle geometry on the penetration behaviour is considered.
Finally, a link is made between the replication fidelity and
the penetration behaviour by modifying the holding pres-
sure during injection moulding and by modifying the poly-
mer material.
Fig. 1  Cross-hatching laser strategies for a circular and b oval base shapes
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
2 Materials and methods
2.1 Materials
Two thermoplastic materials are used in this study: a poly-
carbonate (Lexan™ HP1HFEU, Sabic, Saudi Arabia) and a
glass fibre–reinforced polypropylene (Fibremod™ GB311U,
Borealis, Austria). The polycarbonate material is a biocom-
patible grade with high stiffness (tensile modulus, 1 mm/
min, 2300 MPa). The glass fibre–reinforced polypropyl-
ene is chosen for its combination of high flowability (MFR
230 °C/2.16 kg, 2.0 g/10 min) and stiffness (tensile modu-
lus, 1 mm/min, 7000 MPa). The mould material is a low
corrosion tool steel Stavax (grade 1.2083–AISI 420–DIN
X42Cr13), which is widely used in the mould industry
because of its high corrosion and wear resistance.
2.2 Methodology
2.2.1 Laser scanning strategy
The microneedle cavities in the mould are fabricated with
a Lasea LS5 machine equipped with a femtosecond laser
source (Satsuma HP, Amplitude Systemes, France). The
laser emits pulses of 250 fs with a maximum power on target
of 7.7 W. The focal length of the focusing lens is 100 mm.
The Gaussian beam has a beam focus radius of 8.2 µm [16].
The pulse repetition rate is set to 500 kHz, and the pulse
energy is 15.4 µJ, corresponding to an average fluence of
7.3 J/cm2. A cross-hatching laser strategy with a circular
and oval scanning area is used for the creation of the mould
cavities, as shown in Fig. 1. In these strategies, the laser
covers the scanning area (represented by the dotted line) in
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
parallel lines, and the direction of the lines is changed by 90°
at every layer. The scan-free area (SFA) is the area where no
laser pulses are delivered. This creates a pillar in the HMN
cavity, which ensures that the replicated microneedles are
hollow. The hatch pitch is the distance between two parallel
lines, and the layer pitch is the downward movement of the
laser beam focus after every layer. The eccentricity is the
centre-to-centre distance between the SFA and the scanning
area.
2.2.2 Laser machining experiments and µ‑CT scanning
Three sets of experiments are performed in order to gain
insights in different aspects influencing the hollow micronee-
dle geometry and to design hollow microneedles suited for
penetration and intradermal fluid injection or extraction.
A schematic representation of the overall methodology is
shown in Fig. 2. The first set of experiments is designed to
study the influence of the shape and size of the scan-free
area on the HMN geometry and comprises six laser scanning
strategies with various scan-free area geometries. Those
lasered cavities are analysed with micro-computed tomog-
raphy (µ-CT), and the outcome is used to design the second
set of experiments. Set 2 is designed to study the influence
of various laser scanning parameters on the HMN geom-
etry. These HMN cavities are analysed with µ-CT, and the
cavities with full lumen-forming pillars (i.e. the top of the
lumen-forming pillar is in plane with the mould surface) are
repeated on a separate mould insert for replication with PC
and penetration analysis with an artificial skin model. In set
Fig. 2  Schematic representation
of the methodology
535
2, the injection moulding holding pressure is limited by the
needle deformations occurring for inserts with high numbers
of needles. Therefore, a selection of 6 HMN geometries is
made for set 3, where the holding pressure can be increased.
The selection of the HMN geometries is based on the results
of the penetration tests of set 2. These six selected laser strat-
egies are repeated on another mould insert, then replicated
with PC at high holding pressure and glass fibre–reinforced
polypropylene (GFR-PP), which has high flowability and
stiffness. Additionally, penetration tests are performed with
these six replicated HMNs in the artificial skin model.
A schematic representation of the laser strategies used
in this study is shown in Fig. 3. The scanning speed, hatch
pitch, and layer pitch are kept constant for all experiments
at 100 mm/s, 15 µm and 2 µm, respectively. In the first set
of experiments, six variations of the shape and dimensions
of the scan-free area are produced, each repeated four times
for repeatability assessment. Set 1 consists exclusively of
circular base shapes. The position of the different SFAs is
given in Fig. 3a by the shortest distance between the edge
of the SFA and the scanning centre. In the second set of
experiments, two different base geometries are used, being
circular (Fig. 1a) and oval (Fig. 1b), both including a circular
scan-free area. The oval shape consists of a half circle with
radius 1, and a half ellipse with radius2 = radius1 × 1.2 on
the side of the SFA. The other varied scanning parameters
are the diameter, eccentricity, SFA diameter, and number
of layers to create cavities with every possible combination
of these parameters, with the exception of the combina-
tion of scanning diameter and SFA diameter of 400 µm and
536
Fig. 3  Overview of the laser scanning strategies for set 1 (a), set 2 (b), and set 3 (c)
150 µm, respectively. In total, the second set of experiments
comprises 90 different HMN cavities. The laser strategies
with the combination of diameter 1 = 400 µm and SFA diam-
eter = 150 µm were omitted due to the large proportion of
scan-free area to ablation area. In the third set of experi-
ments, six selected scanning strategies from set 2 (S1–S6)
were lasered in 2 × 2 arrays in a new mould insert, compris-
ing a total of 24 HMN cavities on the mould insert.
For µ-CT analysis, the lasered inserts are cut with
wire-electrical discharge machining (EDM) into strips of
4 × 4 × 50 mm and analysed with a Phoenix Nanotom micro-
computed tomography (µ-CT) system. Each scan consists
of 2400 images and is taken with the “fast-scan” function
active. The acquisition parameters are as follows: cur-
rent = 80 μA, voltage = 120 V, and voxel size = 4 µm. GE
phoenix datos|x REC is used as reconstruction software to
generate slices, and the slices are analysed with Fiji ImageJ.
A typical slice through the centre of a HMN cavity is shown
in Fig. 4a, depicting the cavity depth, the depth of the lumen-
forming pillar, and the depth of the ridge-forming trench.
The orientation of the slice is highlighted in Fig. 4b. The
depth of the lumen-forming pillar is defined as the distance
between the mould surface and the top of the standing pillar
resulting from the SFA. To ensure the functionality of hol-
low microneedles, it is essential to minimise the depth of
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
the lumen-forming pillar. A significant depth of the lumen-
forming pillar may lead to needle clogging, rendering it non-
functional. The ridge-forming trench is the ablated material
between the lumen-forming pillar and the outer edge of the
cavity.
2.2.3 Replication with injection moulding
The injection-moulded part selected for this study is a
55 × 60 × 1 mm flat plate. The polymer is injected through a
hot runner located 17 mm from the edge of the product. The
lasered microneedle cavities are located on a 16 × 16 mm
insert, which is centred horizontally on the product and posi-
tioned 3 mm from the edge, opposite to the gate, as depicted
in Fig. 5.
The injection moulding experiments are conducted on a
hydraulic injection machine (ES 200/35 HL, Engel, Austria)
with a maximum clamping force of 350 kN and a 25-mm
horizontal screw. The cooling time is kept at 15 s for all
experiments. The barrel temperature is set to the highest
recommended value provided by the polymer manufacturer.
The volumetric injection rate is set to the highest achiev-
able value of the injection moulding machine. The holding
pressure and temperature are varied throughout injection
moulding experiments to find the highest possible value,
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
Fig. 4  a Central µ-CT slice of a hollow microneedle cavity. b Isomet-
ric view of a cavity with highlighted orientation of the µ-CT slice
Fig. 5  Schematic representation of a the top and b the side view of
the mould cavity. All units are millimetre
without causing injection moulding defects. An increased
mould temperature will delay the formation of the poly-
mer solidification, which improves the replication fidelity
[17]. However, an excessive mould temperature can lead to
defects such as needle deformation (Fig. 6), where the needle
is stretched, characterised by a decrease in diameter close to
537
Fig. 6  Deformed hollow microneedle
the needle base. The injection moulding process parameters
are shown in Table 1.
For the geometrical assessment of the needles, the poly-
mer plates are cut into 2.5 × 2.5 mm squares with nine nee-
dles each. From these nine needles, all but the central one
are scraped off the plate using a surgical knife, resulting in
a single needle surrounded by around 1 mm of base plate on
either side. In this way, the central needle is not damaged by
the cutting process. The isolated needles are then analysed
with a digital microscope (VH-S30, Keyence, Japan), and
the needle length, tip wall thickness, tip radius, ridge height,
and tip angle are measured with the built-in measurement
software. Figure 7 shows different views of a replicated
HMN.
2.2.4 Penetration tests
The penetration tests are designed to gain insights into the
mechanisms of skin piercing and to compare the different
HMN geometries to each other. As a skin surrogate, a
30 × 30 × 20 mm block of 1 m/v% agarose gel covered by
one layer of Parafilm® is used in this comparative study
because of its high repeatability and similitude to human
skin [18]. In this skin model, which is an adaptation of
the skin model used by Koelmans et al. [11], the Para-
film® layer acts as the stratum corneum, and the agarose
gel acts as the dermis. While it is crucial to acknowledge
that the measured penetration forces using the artificial
skin model are anticipated to deviate from those in vivo
in human skin, it is important to clarify that the intention
is not to replicate human skin. The purpose of employing
an artificial skin model is solely to facilitate a compara-
tive analysis of the puncture behaviour exhibited by vari-
ous needles, allowing for the identification of key factors
538 The International Journal of Advanced Manufacturing Technology (2024) 132:533–551

Table 1  Injection moulding Set 1; PC Set 2; PC Set 3; PC Set 3; GFR-PP

parameters for the replication
of HMNs Barrel temperature (°C) 315 315 315 260
Volumetric injection rate ­(cm3/s) 149 147 147 147
Holding pressure (bar) 749 316 633 550
Mould temperature (°C) 115 115 115 110

Fig. 7  Replicated HMN. a 3D-view of the needle on its base plate. b 3D-view for tip wall thickness measurement. c Front view. d Side view

influencing the penetration force of HMNs. For the pen-
etration tests, a motorised tension and compression tester
(BZ2.5/TS1S, Zwick, Germany) equipped with a 500-N
load cell is used. The agarose gel was laid in a 3D-printed
case and the Parafilm® layer is maintained in place with
two clamps. For every needle, five penetration tests are
conducted, each on the same set of agarose gel and Para-
film®, but at different locations. One combination of aga-
rose gel and Parafilm® is used for approximately four nee-
dles in total, which corresponds to 20 penetration cycles.
To compensate for the variability in the different sets of
agarose gel and Parafilm® layer due to different tension
in the Parafilm® layer or different humidity levels in the
agarose gel, the force measurements are recorded relative
to the penetration force of one needle geometry, which is
used on every artificial skin set. The penetration tests are
also performed with commercially available 34G needles,
which have been reported to penetrate human abdominal
skin at 0.17 N [19], to assess the similitude between arti-
ficial and human skin.
The penetration testing procedure is as follows:
1. Place the (artificial) skin model underneath the down-
ward facing needle.
2. Reduce the distance between the needle and the top
surface of the artificial skin at 1 mm/min until contact
(threshold of 0.01 N).
3. Once contact is made, lower the head at a speed of
2 mm/min until 0.4 N is reached while recording the
force and displacement every 1 µs.
4. Retract the head to the start position (i.e. above the arti-
ficial skin).
The low insertion speed of 2 mm/min is chosen experi-
mentally to ensure sufficient resolution of the force–dis-
placement measurements. After conducting the penetra-
tion tests, the needles were visually inspected using a
digital microscope. None of the needles exhibited any
evidence of deformation following the penetration tests.
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551 539

3 Results and discussion

3.1 Set 1: variation of the SFA shape and size

Figure 8 shows the cavity depth, the depth of the ridge-

forming trench, and the depth of the lumen-forming pillar
(see Fig. 4) for the six respective laser strategies. It is
clear that strategies with a smaller distance between the
SFA and the scanning centre result in shallower cavities.
This is a direct consequence of the reduced number of
pulses towards the centre of the cavity, leading to less
ablation. Also, the depth of the lumen-forming pillar,
which should be minimised to prevent needle clogging,
is influenced by the size of the SFA. Figure 9 shows the
depth of the lumen-forming pillar in function of the diam-
eter of the incircle (i.e. the largest circle fitting inside the
Fig. 9  Influence of the incircle diameter on the depth of the lumen-
SFA geometry).
forming pillar. The error bars represent the standard deviation on the
It is clear that smaller incircles, regardless of the shape depth
of the SFA, result in larger depths of the lumen-forming
pillars. The laser ablation of the top of the lumen-form-
ing pillar is due to the fact that the laser focus is lowered The depth of the ridge-forming trench follows a simi-
after every scanned layer. In doing so, the beam is focused lar trend to the cavity depth, increasing with smaller SFAs
towards the bottom of the cavity, but defocused on the top (Fig. 8). This can be explained by the fact that a smaller
surface of the mould. The interaction between the defo- SFA leads to more energy deposition to the material, which
cused beam and the lumen-forming pillar leads to ablation results in a deeper cavity and ridge-forming trench. When
of the latter. By increasing the incircle of the SFA, the only looking at the ridge-forming trench, it can be con-
accumulated fluence on the centre of the lumen-forming cluded that smaller SFAs are beneficial for the HMN geom-
pillar is lowered. This graph also shows a saturation phe- etry because they lead to deeper ridge-forming trenches,
nomenon at 80 µm, where the depth of the lumen-forming which will prevent the replicated needle from leaking when
pillar is close to 0 µm. Above 80 µm, an increase of the inserted into the skin. However, larger SFAs are desired to
incircle diameter does not lead to a decrease of the depth obtain full lumen-forming pillars. Therefore, the optimal
of the lumen-forming pillar. It is expected that this satu- HMN strategy is expected be a compromise between low
ration point is dependent on the number of layers, as this depth of the lumen-forming pillar and large ridge-forming
influences the defocusing of the laser beam. trench.

Fig. 8  Influence of the SFA shape and size on a the cavity depth, b the depth of the ridge-forming trench, and c the depth of the lumen-forming
pillar. No ridge-forming trench could be found for the scanning strategy on the right. The error bars represent the standard deviation
540
3.2 Set 2: variation of different laser scanning
strategy parameters and penetration tests
3.2.1 Variation of the base geometry, SFA size and position,
scanning diameter, and number of layers
In this set of experiments, a number of laser scanning param-
eters are independently varied, and their influence on the
cavity shape and HMN penetration performance is analysed.
Examples of cross-sectional views obtained from the µ-CT
measurements at the centre of the HMN cavities are shown
in Fig. 10. Cone-shaped hollow microneedle cavities with
very small tip radii (a few micrometres) are observed for all
sets of laser parameters. However, the shape and dimensions
vary between the different microneedle cavities. The influ-
ence of the laser strategy parameters on the geometry of the
HMN cavities is discussed in the following section.
Figures 11, 12, and 13 show the evolution of the cavity
depth, the depth of the ridge-forming trench, and the depth
of the lumen-forming pillar for circular and oval laser strate-
gies with small and large SFA for varying number of lay-
ers, eccentricity, and scanning diameter, respectively. Each
datapoint represents the average value over the numbers of
layers, eccentricities, or scanning diameters.
The cavity depth is generally increased by an increasing
number of layers due to the higher accumulated fluence.
However, the increase in depth is lower at higher numbers
Fig. 10  Influence of the laser scanning parameters on the cavity shape. Example starting with a circular base shape with the independent varia-
tion of each of the scanning strategy parameters. The µ-CT slices are taken at the centre of the HMN cavities
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
of layers. This is caused by the fact that deeper cavities have
steeper walls, resulting in (i) the distribution of the laser
spot over a larger surface, leading to a minimised ablation,
and (ii) a larger portion of the scanning area being out of
focus. These two phenomena result in a decrease of the
ablation efficiency for high aspect ratio cavities. A similar
trend has also been reported by Evens et al. [20] for solid
microneedles. There is no noticeable difference in cavity
depth between oval and circular shapes. Indeed, the two laser
strategies are designed in such a way that the central abla-
tion zone (read: the scanning zone on the right of the SFA
on Fig. 1) is similar for oval and circular cavities. Figure 11a
also shows similar cavity depths for different SFA diameters.
This shows that the influence of the SFA diameter on the
cavity depth is negligible in the tested range.
The depth of the ridge-forming trench is generally
increased by a higher number of layers, with a similar satura-
tion effect as for the cavity depth. The ridge-forming trench
is deeper for oval base shapes than for circular ones, which
is expected since oval base shapes have a larger scanning
area between the SFA and the edge of the scanning diameter.
Also, the saturation effect is larger for circular base shapes
than for the oval ones. This is due to the smaller width of
the ridge-forming trench in the circular strategy, leading to
trenches with steeper walls and higher aspect ratios. The
depth of the ridge-forming trench is larger for the small
scan-free areas (100 µm) than for the large SFA (150 µm).
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
Fig. 11  Influence of the number of layers on a the cavity depth, b depth of the ridge-forming trench, and c depth of the lumen-forming pillar
This shows that the SFA diameter has a larger influence on
the ridge-forming trench than on the cavity depth. In fact, the
relative increase in SFA diameter over scanning area diam-
eter is larger on the side of the ridge (left of the SFA) than
on the central side (right of the SFA), leading to a higher
influence on the ridge-forming trench.
The depth of the lumen-forming pillar is, as was men-
tioned in Sect. 3.1, mainly influenced by the diameter of
the SFA. Figure 11c shows that large scan-free areas result
in full lumen-forming pillars, with depths equal or close to
zero. This means that the top of the lumen-forming pillar is
in plane with the top surface of the mould insert. Concerning
the small SFA, an increase in number of layers results in a
deeper lumen-forming pillar. This is caused by the fact that
the focus point of the laser is lowered at every layer, which
means that the beam is increasingly defocused on the top
surface. Hence, its ablation area increases and it can ablate
further away from the beam centre, leading to more ablation
of the lumen-forming pillar. The depth of the lumen-forming
pillar is larger for the oval laser strategy than for the circular
one. This is a result of the enlarged ablation zone in the oval
strategy leading to more pulses around the SFA which, when
defocused, ablate the lumen-forming pillar.
541
Figure 12a shows that a larger eccentricity results in a
deeper cavity. This is expected, since a larger eccentricity
means that more energy is delivered towards the centre of
the cavity, which increases the needle depth. Overall, the
circular strategy results in slightly deeper cavities than the
oval one. On average, the difference in cavity depth between
circular and oval strategies equals to 68 µm, which corre-
sponds to only 4% of the average cavity depth and can thus
be neglected. In Fig. 12b, it is clear that the eccentricity has
a large influence on the depth of the ridge-forming trench.
Namely, the larger the eccentricity, the smaller the ridge-
forming trench. This is a direct result of the reduction of
scanning area between the SFA and the edge of the scan-
ning zone. Figure 12c shows the difference in depth of the
lumen-forming pillar between small and large SFA, as dis-
cussed for Fig. 11c. Besides this, it does not show a particu-
lar trend for the influence of the eccentricity on the depth of
the lumen-forming pillar. The relatively small differences at
SFA 100 µm can be attributed to material impurities, laser
scanning variability, and measurement uncertainties.
Figure 13 shows the influence of the scanning diameter on
the cavity depth, the depth of the ridge-forming trench, and
the depth of the lumen-forming pillar for circular and oval
542
Fig. 12  Influence of the eccentricity on a the cavity depth, b depth of the ridge-forming trench, and c depth of the lumen-forming pillar
laser strategies with small and large SFA. No datapoint can
be found for large scan-free areas and a scanning diameter
of 400 µm because this combination of parameters was ruled
out of the experiments due to its high SFA to diameter ratio
(see Sect. 2.2.2). Each datapoint represents the average value
over the different numbers of layers and eccentricities.
Figure 13a shows that the cavity depth increases with an
increasing scanning diameter. This is a result of the fact that
wider cavities have less steep walls, resulting in less reflec-
tion and a lower dispersion of the laser energy. Hence, wider
cavities absorb more laser energy, which increases their
depth. This was also noticed by Evens et al. [20] for solid
microneedle cavities. Also, the depth of the ridge-forming
trench (Fig. 13b) increases with an increasing scanning
diameter. This is also a result of the lower energy absorp-
tion for steeper slopes. Figure 13c shows that the depth of
the lumen-forming pillar decreases for increasing scanning
diameters for the small SFA. This is possibly caused by inac-
curacies of the laser scanner, which accelerates and deceler-
ates at the beginning and end of every scanning line, leading
to discrepancies in the pulse spacing. Since at small scan-
ning diameters, the scanner quickly accelerates then deceler-
ates, the pulse deposition accuracy is more largely affected.
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
This negative dynamic effect can be compensated in the
laser controller software [21]. However, it can be assumed
that this compensation was not seamless.
Figure 14 shows the influence of the number of layers
on the cavity diameter for circle and oval base shapes with
small and large SFA and various scanning diameters. Each
datapoint represents the average value over the different SFA
diameters and eccentricities.
It is clear that an increasing number of layers gener-
ally leads to a larger cavity diameter. As explained in
Sect. 2.2.1, every layer is followed by a downward move-
ment of the laser focus corresponding to the layer pitch.
This results in an approximately focused beam towards
the centre of the cavity, but defocused beam on the cav-
ity edges, where the beam interacts with the top surface
of the mould insert. If the laser fluence of the defocused
beam surpasses the ablation threshold on the top surface,
ablation occurs and the cavity is widened. Figure 14 also
shows that the cavity diameter, even at 150 layers, is larger
than the programmed scanning diameter. Indeed, with the
focused spot size being around 20 µm, the effective cavity
diameter is expected to always be at least 20 µm larger
than the scanning diameter, which corresponds to the
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551 543

Fig. 13  Influence of the scanning diameter on a the cavity depth, b depth of the ridge-forming trench, and c depth of the lumen-forming pillar

Fig. 14  Influence of the number

of layers on the cavity diameter.
For oval base shapes, the pro-
grammed short axes are 400,
500, and 600 µm, and their cor-
responding long axes are 440,
550, and 660 µm, respectively

measured values. It is worth highlighting that, in accord- 3.2.2 Replication

ance with the defined parameters of the oval laser strat-
egy, the length of the oval’s long axis consistently exceeds
that of its short axis. Finally, the diameter of the circular
cavities and the short axis of the oval cavities are nearly
indistinguishable, which is an obvious result of the design
of the laser strategies.
The analysis of the µ-CT slices showed that the top surface
of the lumen-forming pillar of some HMN cavities is located
under the top surface of the mould insert (see Fig. 10). In
order to ensure optimal functionality of the HMNs, it is
crucial that the top of the lumen-forming pillar is in plane
544
with the surface of the insert. Out of the 90 lasered HMN
cavities, 21 cavities with circular scanning shape and 38
cavities with oval scanning shape fulfil this requirement. The
59 (21 circular + 38 oval) corresponding laser strategies are
selected for the replication phase and subsequent penetration
tests. The overall replication fidelity, defined as the repli-
cated needle length divided by the cavity depth, is on aver-
age 82 ± 7%. The replication fidelity of the ridge-forming
trench is on average 48 ± 20%, which is considerably lower
than the overall replication fidelity. This difference in rep-
lication fidelity is caused by the fact that the aspect ratio of
the ridge-forming trench is higher than that of the overall
cavity. This increased surface/volume ratio leads to a faster
freezing of the polymer and thus a lower replication fidelity.
A similar relationship between aspect ratio and replication
fidelity was noted by Evens et al. [22]. Figure 15 shows the
influence of the eccentricity on the overall replication fidel-
ity as well as the replication fidelity of the ridge-forming
trench. Each datapoint represents the average value over the
different scanning diameters, scanning shapes, numbers of
layers, and SFA diameters.
Fig. 15  Influence of the eccentricity on the replication fidelity of the
main cavity and ridge. The error bars represent the standard devia-
tions
Fig. 16  Force–displacement
graphs for a successful and b
unsuccessful penetration of
a HMN in the artificial skin
model
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
The downward trend of the replication fidelity of the
ridge shows that the position of the SFA influences the fill-
ing behaviour of the ridge-forming trench. Indeed, a higher
eccentricity leads to a narrower ridge with faster cooling of
the polymer. The overall replication fidelity, however, is not
impacted by the eccentricity, as the displacement of the SFA
is minimal compared to the width of the main cavity.
3.2.3 Penetration
Throughout the penetration tests, both successful and unsuc-
cessful penetrations were observed. The penetration event is
defined by a sudden decrease in force, as described in [23,
24]. Typical force–displacement graphs for HMNs with suc-
cessful and unsuccessful penetration are shown in Fig. 16.
For successful penetrations, the penetration graph can
be divided into three phases: (I) the force build up at the
needle tip, (II) the penetration event, which is characterised
by a sudden drop in force or a plateau, and (III) the second
force build up due to the contact between the base plate and
the skin model. The penetration force is determined as the
maximum force reached at the junction of phase I and II. For
unsuccessful penetrations, the base plate comes in contact
with the skin model before the penetration event, and only
two phases can be discerned: (I) the force build up at the
needle tip and (II) the second force build up due to the con-
tact between the base plate and the skin model.
Figure 17 shows the penetration success rate in the artifi-
cial skin model for every replicated circular and oval needle
in function of its length. Every needle is tested five times
for penetration on the artificial skin model. A penetration
success rate of 1 corresponds to five successful penetrations
out of five.
It is clear that the length of a needle has a large influence
on its penetration success rate. Figure 17 shows that needles
shorter than 1095 µm do not penetrate the skin model, while
needles above this threshold have varying penetration suc-
cess. This is linked to the fact that for short needles, the force
at the needle tip cannot reach a sufficiently high level before
contact between the base plate and the artificial skin is made.
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551 545

In the following analysis, only the needles with length higher

Fig. 17  Influence of the needle length on the penetration success rate
Fig. 18  Influence of the tip angle on the penetration force. The error
bars and the shaded area represent the standard deviations on the
penetration force. The dashed line represents the linear regression of
the datapoints with successful penetration and R is the linear correla-
tion coefficient. Datapoints with a penetration force of 0 N represent
unsuccessful penetrations
than 1095 µm are depicted. The average penetration force
of the oval and circular HMNs in function of the tip angle is
shown in Fig. 18, together with the average penetration force
of the 34G needle with identical skin model.
This figure shows that when successful penetration
occurs, the tested needles require forces between 0.17 and
0.30 N for penetration. Also, a larger tip angle generally
results in a higher penetration force. Indeed, a low tip angle
results in highly localised pressure on the skin, leading to
high stress and faster penetration. In Fig. 19, the side views
of three different HMN geometries are shown. Figure 19a
and b clearly show the differences between HMNs with
low and high tip angles, respectively. Figure 19c depicts a
HMN with a low tip angle, yet without penetration success
caused by the particular tip geometry. While the tip angle,
as depicted by the white dotted lines, is relatively small,
the needle surface in contact with the skin model increases
rapidly during the penetration test, leading to a decrease in
localised pressure and thus an unsuccessful penetration.
When comparing the penetration results from the injec-
tion-moulded HMNs with the commercially available 34G
needle (Terumo, Japan), it can be noticed that the injection-
moulded HMNs require 3.5 to six times more force to pen-
etrate the same skin model. However, it is important to note
that the 34G needles used in this study are stainless steel
hypodermic needles. They have a different bevel geometry
than the injection-moulded HMNs and have a length of
4 mm. While their penetration force is low, their relatively
long length makes them unsuitable for intradermal injection.
In Fig. 20, only the datapoints with successful penetration
are analysed, and the influence of the tip radius and tip wall
thickness on the penetration force are studied.
Figure 20a shows that a larger tip radius typically leads
to an increase in penetration force due to an increase in con-
tact area between the needle and skin model. Figure 20b,

Fig. 19  Side view of three

different HMN geometries. a
Relatively small tip angle (30°)
and low penetration force (0.19
N). b Large tip angle (43°)
and no penetration success. c
Relatively low tip angle (36°)
and no penetration success due
to its particular tip geometry.
The dotted lines represent the
tip angles
546 The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
however, does not show any significant relationship between
the tip wall thickness and penetration force within the tested
range. This lack of trend is unexpected, since the tip wall
thickness has a direct impact on the surface in contact with
the artificial skin during penetration. However, it could be
explained by the relatively short range of tip wall thicknesses
measured (34–62 µm). In the following section, it can be
seen that the tip wall thickness can be influential for the
penetration force when the range of tip wall thicknesses is
increased.
The penetration results show that a minimum needle
length is required for successful penetration of the HMNs,
and Sect. 2.2.1 shows that the depth of the HMN cavity is
positively influenced by the number of layers, eccentricity,
and scanning diameter. Another determining factor for the
penetration force is the tip angle. The tip angle can be cor-
related to the difference between the needle length and the
ridge height. The ridge height is a result of the depth of
the ridge-forming trench and the replication fidelity of the
ridge. The depth of the ridge-forming trench increases with
increasing number of layers and scanning diameter and with
decreasing eccentricity. Interestingly, the eccentricity doubly
affects the ridge height through its influence on the depth
of the ridge-forming trench and on the replication fidelity
of the ridge.
Drawing from the findings above, a laser scanning strat-
egy can be designed for a minimised tip angle: the eccen-
tricity and scanning diameter should be maximised, while
the number of layers should be chosen so that the minimal
required needle length is reached and the ridge is minimised.
However, this scanning strategy does not take into account
other functional necessities of HMNs such as the fact that
functional HMNs require a significant ridge in order to pre-
vent leakage, or that the distance between the top surface of
the lumen-forming pillar and the mould surface should be
minimised. Leakage is a non-negligible issue for intradermal
injection and extraction [25], and tests with a more appropri-
ate skin model should be performed to determine the mini-
mum required ridge height for leak-free injections. Although
the depth of the lumen-forming pillar would increase in the
Fig. 20  Influence of a the tip
radius and b the tip wall thick-
ness on the penetration force.
The error bars and the shaded
area represent the standard devi-
ations on the penetration force.
The dashed line represents the
linear regression and R is the
linear correlation coefficient
case of an increase in number of layers, it could be countered
by an increase in scanning diameter and SFA diameter.
It is important to note that the interactions between the
laser scanning parameters, injection moulding process, and
penetration force are multiple. An example is the two-way
impact of the eccentricity on the penetration force. Firstly,
a high eccentricity reduces the tip angle, therefore reducing
the area of contact between needle and skin and leading
to a lower penetration force. Secondly, higher eccentricity
means more ablation towards the centre of the cavity, which
eventually gives more room for the injected polymer to flow
towards the bottom of the cavity and thus form a sharper tip.
Based on the above results, a selection of six HMNs
is made for replication with improved injection moulding
process (i.e., higher holding pressure) and further penetra-
tion tests. As mentioned in Sect. 2.2.2, the lower number
of cavities on the mould insert of set 3 enables the use of
higher holding pressure without needle deformations. The
HMN selection includes one circular and one oval needle
with low penetration forces (S2, S6), two needles with suc-
cessful penetration and a high ridge (S1, S5), and two short
needles (< 1095 µm) with unsuccessful penetration but a
low tip angle, tip wall thickness, and tip radius (S3, S4).
These needles and their corresponding penetration forces
are depicted in Fig. 21.
3.3 Set 3: variation of the injection moulding
process and penetration tests
3.3.1 Replication
Needles S1–S6 are replicated with PC using both a high and
low holding pressure and GFR-PP. Their lengths and ridge
heights are depicted in Fig. 22. Figure 22a shows an increase
in length for the replicated PC needles with higher holding
pressure. Indeed, a higher holding pressure forces the poly-
mer material deeper into the HMN cavities. The replication
with GFR-PP leads to even longer HMNs. This discrep-
ancy in overall replication fidelity across materials can be
a result of four factors, namely linear shrinkage, interfacial
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551 547

Fig. 21  Selection of six different needle geometries for improvement of the injection moulding process and replication with GFR-PP and PC

wetting behaviour, creep deformation behaviour, and melt
viscosity, as discussed by Evens et al. [20]. This increase in
replication fidelity can also be noticed in Fig. 22b, where
the ridges of the PC needles with high holding pressure are
higher than those with low holding pressure in all but one
case, and the ridges of the GFR-PP needles are the high-
est. A similar reasoning to the needle height can be applied
for the ridge height, where a higher holding pressure and a
higher flowability, better wettability, and slower solidifica-
tion rate increase the filling of the microcavities. For needles
S3 and S4, it is important to note that, even with the better
replication settings, they are still shorter than 1095 µm,
which was reported as the lower length limit for penetra-
tion (Sect. 3.2.3). Therefore, they can be expected to yield
unsuccessful penetration.
Figure 23 shows the evolution of the tip geometry fea-
tures for different holding pressures and polymer materi-
als. Contrary to the evolution of the needle length and ridge
height, no recurring trend can be found for the evolution
of the tip angle, tip radius, and tip wall thickness. The tip
angle is generally largest for the GFR-PP needles and can
be linked to the large increase in ridge height compared to

Fig. 22  Evolution of the a needle length and b ridge height for PC with low holding pressure (denoted by ‘low P’ in the legend), PC with high
holding pressure (‘high P’ in the legend), and GFR-PP
548
the relatively small increase in needle length for GFR-PP.
The tip radius varies significantly across the different nee-
dles and injection moulding parameters, without any signifi-
cant trend. The range of the measured tip wall thicknesses
is extended with this set of experiments, with a number of
needles with tip wall thickness smaller than 30 µm, even as
low as 15 µm. When looking at the cavity shape, one could
expect the tip wall thickness to be inversely proportional to
the overall replication fidelity, due to the conical nature of
the cavity. However, this trend cannot be confirmed from the
data shown in Figs. 22a and 23c.
3.3.2 Penetration
Figure 24 shows (a) the products of tip wall thickness, tip
radius, and tip angle and (b) a comparison of the forces
required to penetrate the artificial skin model for the differ-
ent HMNs in PC with low holding pressure, PC with high
holding pressure, and GFR-PP. The tip wall thickness, tip
Fig. 23  Evolution of the a tip angle, b tip radius, and c tip wall thickness for PC with low holding pressure (denoted by ‘low P’ in the legend),
PC with high holding pressure (‘high P’ in the legend), and GFR-PP
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
radius, and tip angle are decisive features for the surface area
in contact with the skin during insertion. It can be intuitively
deduced that a low contact area is desired to reduce the pen-
etration force. Indeed, a reduction in contact area leads to a
more localised application of the force and higher stress in
the skin. As a result, the ultimate tensile strength of the skin
can be overcome at a lower penetration force. S3 and S4,
which do not exhibit successful penetration with low hold-
ing pressure in PC, also do not penetrate in the other tested
configurations, even with the increase in needle height noted
in Sect. 3.3.1, and are therefore not shown in the figure.
The products of tip wall thickness, tip radius, and tip
angle do not follow any significant trend across all needles in
function of the tested configurations of the injection mould-
ing process. For needles S1 and S2, the products are not
changed in any major way by the higher holding pressure or
different polymer materials. For needles S3 and S5, there is a
noticeable increase for both PC with higher holding pressure
and GFR-PP compared to PC with low holding pressure. For
The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
Fig. 24  Evolution of a the product of the tip wall thickness, tip
radius, and tip angle and b the penetration force for PC with low
holding pressure (denoted by ‘low P’ in the legend), PC with high
needle S4, the product of geometrical tip features decreases
for a higher holding pressure and for GFR-PP. Needle S6
sees a large decrease for the higher holding pressure and a
major increase for GFR-PP compared to PC with low hold-
ing pressure.
From Fig. 24b, it can be seen that for S1 and S2, no
significant change in the penetration force is observed
between the three configurations. The penetration force
of S5 increases with high holding pressure in PC and with
GFR-PP. Meanwhile, S6 penetration force decreases in PC
with high holding pressure due to a larger increase in ridge
height compared to needle height. In contrast, S6 penetration
force increases in GFR-PP compared to PC with low holding
pressure. These trends align with observations in Fig. 24a,
where the product of tip wall thickness, tip radius, and tip
angle indicates that tip wall thickness is a significant factor
influencing penetration force, especially when considering
a broader range of measured tip wall thicknesses.
A better overall replication fidelity was expected to
result in a sharper needle and lead to a lower penetration
force. However, this trend cannot be confirmed for injec-
tion-moulded hollow microneedles. Indeed, when compar-
ing Figs. 22a and 24, it can be noticed that a higher overall
replication fidelity (i.e. an increase in needle length) can
even result in a higher penetration force when the increase in
ridge height is significantly larger than the increase in needle
length, leading to a larger tip angle and tip radius.
No specific mechanical failure analysis was performed
on the HMNs, but their geometrical features were examined
with a microscope after every penetration experiment (data
not shown). These inspections showed that both the PC and
GFR-PP HMNs could withstand the penetration tests with-
out any visible deformations. The penetration force of a 34G
549
holding pressure (‘high P’ in the legend), and GFR-PP. The error bars
represent the standard deviations
needle in the artificial skin model is measured at 49 ± 3 mN,
while the penetration force of the same needle in human sub-
jects (on the side of the abdomen) was reported between 160
and 190 mN [19]. This indicates that the penetration force
obtained using the artificial skin model could be underesti-
mated by up to three times. As a consequence, all needles
tested in this study might not be suited to pierce human skin
due to possible structural constraints leading to mechani-
cal failure during insertion. However, the approach remains
suitable for studying the mechanisms of HMN insertion and
the relationships between fs laser ablation strategy, injec-
tion moulding, and needle geometry. Also, for closing the
gap to real-world applications, it is important to consider
biocompatibility and sterilisation possibilities of the chosen
polymer.
4 Conclusion
In this work, three sets of experiments were performed with
injection-moulded polymeric HMNs replicated using fs
laser-ablated moulds. A number of laser scanning param-
eters were varied, being the scanning base shape, the shape
and size of the scan-free area, the number of layers, the
eccentricity, the scan-free area diameter, and the scanning
diameter. The results showed that the laser scanning strate-
gies produced sharp-tipped cone-like cavities with a stand-
ing pillar and that their morphologies are greatly affected
by the laser scanning strategy parameters. The replicated
needles were tested for penetration in an artificial skin model
consisting of agarose gel and a Parafilm® layer. The penetra-
tion tests showed that a minimum needle length is required
to achieve successful penetration and that the combination
550 The International Journal of Advanced Manufacturing Technology (2024) 132:533–551
of tip angle, tip radius, and tip wall thickness is a good indi-
cator of the penetration force. The results indicate that the
needle length and tip angle can be improved with a higher
eccentricity and scanning diameter, while the number of lay-
ers should be chosen so that the needle length is sufficient
while the ridge height remains low. However, it is impor-
tant to note that, while minimising the penetration force,
this strategy does not take into account the potential leak-
age resulting from a HMN with low ridge, or the potential
needle clogging resulting from an excessive depth of the
lumen-forming pillar. It has also been demonstrated that an
increase in overall replication fidelity (i.e. only considering
the needle length and cavity depth) could not be directly
related to lower penetration force due to the change in repli-
cation fidelity, leading to variations of the tip angle.
This comparative study demonstrated the importance of
HMN morphology and highlighted the potential of injection
moulding with laser-ablated moulds for the manufacturing
of functional hollow microneedles. It should be noted that,
although single needle configurations were studied in this
work, HMNs are typically arranged in arrays to increase the
throughput and to target a larger area [26]. The configuration
of the array and skin model, such as the spacing between the
needles, the skin pretension, or the presence of a solid base
layer, was reported to impact the penetration behaviour of
the needle arrays and should therefore be taken into account
for the development of hollow microneedles [27, 28].
Acknowledgements The authors would like to thank Olivier Malek
from Sirris (department of Precision Manufacturing) for the laser abla-
tion of the microneedle cavities. The KU Leuven XCT Core facility
is acknowledged for the 3D image acquisition and quantitative post-
processing tools (https://​xct.​kuleu​ven.​be/).
Author contribution Conceptualization, methodology, and investiga-
tion were performed by Pol Vanwersch and Tim Evens. The first draft
of the manuscript was written by Pol Vanwersch and all authors com-
mented on previous versions of the manuscript.
Funding This work was funded by the KU Leuven Interdisciplinary
Network project IDN/20/011 MIRACLE: Autonomous microfluidic
patch for plasmid-based vaccine, as well as the Fonds Wetenschap-
pelijk Onderzoek (FWO)–Vlaanderen SBO project S003923N and SB
fellowship 1S31022N. The FWO large infrastructure I013518N project
is acknowledged for their financial support of the X-ray infrastructure.
Declarations
Competing interests The authors declare no competing interests.
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