Retinal vessel model fabricated on a curved surface structure for a simulation of microcannulation
Hayakawa et al. Robomech J
Retinal vessel model fabricated on a curved surface structure for a simulation of microcannulation
Takeshi Hayakawa 0
Ippei Kato 0
Fumihito Arai 0
0 Department of Micro-Nano Systems Engineering, Nagoya University , Furo-cho, Chikusa-ku, Nagoya 464-8603 , Japan
A remarkable number of vitreoretinal surgeries are performed each year despite their difficulty. As a result, a high demand exists for a mock-up simulator of retinal vessels to simulate these surgeries. Thus, we propose an artificial retinal vessel model for simulating microcannulation surgery. Using laser lithography, polydimethylsiloxane molding, and hydraulic transfer techniques, we fabricated microchannels approximately ≃10 μm on a 24-mm-diameter curved surface structure that mimics the human eye. In the fabrication, the channel size and wall thickness were controlled to mimic a touch of retinal vessels, which gives important information for microcannulation. We succeeded in fabrication of the proposed model and liquid circulates within the microchannels of this model without leaking. Furthermore, we demonstrated a simulation of microcannulation and measurement of applied force to the model during the simulation using a force sensor placed at the bottom of the model. The results of such experiments are useful to quantitatively evaluate medical techniques.
Surgical simulator; Retinal vessel; 3D microfabrication
Vitreoretinal surgeries have become quite common over
the last few decades. For example, approximately 300,000
operations are conducted annually in Japan, and this
number is predicted to increase because of the aging
population. One such operation is called
microcannulation, which is proposed to patients with central retinal
vein occlusion . In microcannulation, a surgeon inserts
a micropipette into the eyeball and reaches the eye
fundus, which is a curved concave structure (Fig. 1a). Next,
the surgeon finds the occluded vein on the fundus and,
via the micropipette, injects a thrombolytic drug into
the vein to dissolve the clots. This operation requires
mature surgical skills because the retinal vessel is less
than 100 μm in diameter (Fig.1b), This technique is used
despite human hand tremors measuring approximately
100 μm [2, 3]. Furthermore, the retinal vessels lie on the
curved surface and surgeons must find the target
vessel based on their senses of vision and touch. Therefore,
obtaining the skill required to perform microcannulation
surgery takes a long time, and the consequent long
evaluation and training of young doctors is one of the
drawbacks of microcannulation. Another drawback of this
approach is the evaluation of new medical equipment.
Several medical equipment for this difficult surgery, such
as surgical robots, have been proposed in recent years
[4–6]. However, large barriers currently prevent
commercialization of these new instruments, including the
lengthy period required for clinical trials. Thus, a demand
exists for methods to reduce the time to market for such
equipment and shorten the training and evaluation
periods required for surgeons.
At present, training and evaluation of this medical
technique are done with animal samples such as swine eyes
or chick embryos [4–10]. However, structural differences
between individual animal samples are significant, so the
© 2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
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Fig. 1 Central retinal vein occlusion: a schematic of
microcannulation and b optical-microscope photograph of retinal vessels
conditions of evaluation or training differ for each trial.
Furthermore, using such animal samples in an actual
operating room presents contamination risks. Therefore,
a high demand exists for a reproducible method of
evaluating vitreoretinal surgery techniques that can be used in
an actual operating room.
One response to this demand is a surgical simulator.
Basically, two types of surgical simulators exist: a
computer-based virtual reality (VR) simulator [11–15], and a
mock-up simulator made of artificial materials [16–20].
Once electronic data from the target parts are acquired,
the VR simulator can construct the target parts with high
reproducibility. However, mimicking the physical
sensation of touch or the texture of a retinal vessel with the
VR simulator is very difficult, and such sensations are
critical for the surgeon performing vitreoretinal surgery.
Additionally, the effect of new medical equipment on the
human body is difficult to evaluate because interactions
between the human body and medical equipment are too
complex to completely reproduce with current computer
technology. Thus, VR simulators are not suitable for
evaluating medical techniques.
The second approach of a mock-up simulator has the
advantage that it can be physically touched, allowing the
user to learn the requisite sensations of touch or
texture. Mock-up simulators use individual samples that
are highly reproducible because of their well-controlled
fabrication methods. Mimicking blood flow can also be
implemented by circulating a liquid in the vessel models
by connecting them to external tubes and pumps.
Furthermore, selection of appropriate materials allows the
simulator to be sterilized and facilitate the reproduction
of the effects of such medical equipment on the human
body. Thus, mock-up simulators can be used in actual
operating rooms to evaluate the performance of
medical equipment. Therefore, the goal of this research is to
develop a mock-up surgical simulator to allow evaluation
of medical techniques (e.g., surgical skills) or the
performance of medical equipment.
Several studies have already been published discussing
mock-up simulators for various sections of blood vessels
[17–20]. For large vessels (in mm) such as the coronary
artery or arteries in the brain, such simulators can
benefit from 3D printing technology. To simulate
catheterization surgery, Ikeda et al. fabricated a millimeter-sized
3D vessel model made of polydimethylsiloxane (PDMS)
using the lost-wax method [17, 18]. However, fabricating
a model of fine vessels of size below 100 μm (e.g., retinal
vessels) is difficult with this method.
Photolithographybased fabrication techniques can be applied to fabricate
models of smaller vessels. For example, Nakano et al.
fabricated a microchannel that mimics a fine blood vessel
with sizes down to about 10 μm using photolithography
techniques and PDMS molding . Although
photolithography offers sufficient resolution for the retinal
vessel model, it can only be applied to 2D structures. The
target of the present study, however, is to model retinal
vessels of size about 100 μm and that lie on the eye
fundus, which forms a concave curved surface. Therefore,
both the above-mentioned fabrication methods are
difficult to apply in this case (i.e., a retinal vessel model with
microchannels on a curved surface).
We thus propose a retinal vessel model with
microchannels smaller than 100 μm that lie on a concave
curved surface. This retinal vessel model is fabricated
by combining laser-lithography-based fabrication
techniques, PDMS molding, and hydraulic transfer
techniques. Furthermore, the microchannel wall thickness is
controlled with 10 μm accuracy to mimic the physical
human sensation of touching retinal vessels. We circulate
liquid through the fabricated microchannels and
simulate a microcannulation procedure. We also measure the
force applied to the model during the simulated surgery
to demonstrate the usefulness of the proposed model not
only for qualitative evaluation but also for quantitative
evaluation of medical techniques.
Figure 2 shows the concept of the proposed retinal vessel
model, which consists of three layers. The bottom layer is
a curved surface structure (curvature diameter of 24 mm)
that mimics the human eye. The middle layer is a PDMS
sheet with microchannels less than 100 μm in size, which
mimics the structure of human retinal vessels. Finally, the
top layer consists of a thin PDMS sheet, whose thickness
is controlled to within about 10 μm to mimic the
sensation of touching human retinal vessels.
First, microchannels in the middle layer are fabricated
on a PDMS sheet by laser lithography techniques and
PDMS molding. Next, this middle layer is transferred
to the concave bottom layer using a hydraulic
transfer technique. The result is a fine vessel structure
(vessels less than 100 μm in diameter) superposed on the
concave surface. Third, again using hydraulic transfer,
the 10-μm-thick top layer is laid on the middle layer.
Thus, the wall thickness of the top of the microchannels
can be controlled to mimic the sensation of touching a
retinal vessel. Furthermore, the mechanical properties of
the model, such as Youngs modulus or tear strength, can
be tuned by changing the mixing ratio of the base resin
and the curative reagent for PDMS. Therefore, this model
offers both the physical structure of human retinal vessels
and the tactile sensation of touching them.
All parts of the model consist of PDMS or glass, which
can withstand high temperatures and sterilization. As a
result, the model can be used in actual operating rooms.
Additionally, the microchannels can be connected to
external tubes, as shown in Fig. 2a, allowing liquid to
be circulated through the microchannels for
mimicking blood flow. This enables us to circulate liquid in
the microchannel for mimicking blood flow. Thus, the
surgical procedure of injecting thrombolytic drugs into
veins with a micropipette can be simulated with the
proposed model. Furthermore, the force applied during the
simulation can be measured using a force sensor placed
underneath the model. The force information can be
used to quantitatively evaluate medical techniques. We
thus expect the proposed model to strongly contribute to
evaluating surgical techniques or medical equipment and
in the training of surgeons for retinal vessel surgery.
Design of microchannel
First, we designed microchannels for mimicking retinal
vessels based on a shape of real retinal vessels. We
simplified shape of real retinal vessels as shown in Fig. 3 and
determined sized of vessels according to Murray’s law
[21, 22]. Murray’s law states that the cube of radius of a
parent vessel equals the sum of the cubes of the radii of
the daughters, as shown in Fig. 3a and following equation.
We determined the width of first channel (W1) as 150.0
μm (radius: R1 = 75.0 μm), and calculated the width
of second channel (W2) as 119.1 μm (radius: R2 = 59.5
μm) according to Murray’s law. Similarly, we calculated
the width of third and fourth channels as W3 = 94.5
μm (radius: R3 = 47.2 μm), and W4 = 75.0 μm (radius:
R4 = 37.5 μm), respectively.
Mechanical characteristics of PDMS
Second, we confirmed that the mechanical
characteristics of PDMS may be suitably controlled by changing the
mixing ratio of the main resin and curative reagent. In
this study, we focus on Youngs modulus and tear strength
Fig. 2 Conceptual image of retinal vessel model on curved surface: a overview of model, b side view showing line A-A’, and c close-up of side view
Fig. 3 Design of microchannel. a Schematic figure of Murray’s law,
and b actual design and sizes of microchannel
because our target is to simulate microcannulation, and
these two parameters are thought to be strongly related
to the sensation of touching retinal vessels and of
feeling a puncture. Park et al. discussed the controllability
of the mechanical characteristics of PDMS and used this
approach to evaluate surgical skills for a coronary-artery
bypass graft . Although the coronary-artery target
differs from the target of this study (i.e., retinal vessels),
we use the same Youngs modulus and tear strength in
our model as a reference (i.e., 0.13 ± 0.02 MPa and 0.6 ±
0.13 N/mm, respectively).
The Youngs modulus and tear strength were evaluated
based on the Japanese Industrial Standards (JIS) K6251
and K6252, which are equivalent to the International
Organization for Standardization (ISO) 37 and 34. The
dumb-bell test piece 7 and the angle test piece were used
as samples. Each sample was pulled at 200 mm/min and
500 mm/min. We fabricated samples with various
mixing ratios (ratio of curative reagent to main resin) of 10,
20, 33, 50 and 66 wt%. The tensile tests were done three
times for each mixing ratio.
Figure 4a and b show the measured Young’s modulus
and tear strength, respectively. We tuned the Youngs
modulus from 0.14 to 1.14 MPa and the tear strength
from 0.68 to 1.70 N/mm. Considering the target values,
we chose a mixing ratio of 66 wt% for this study.
Furthermore, we performed preliminary sensory testing by
ophthalmologist about sensation of touch and puncture.
By using flat vessel model, we confirmed that the PDMS
with mixing ratio of 66 wt% are the most suitable for
retinal vessel model.
Hydraulic transfer of PDMS sheet
To fabricate a retinal vessel structure on a curved surface,
we hydraulically transferred the PDMS pattern.
Hydraulic transfer is generally used for printing on curved
surfaces [24, 25]. By floating a printed film on water and
pressing a curved surface onto the film, uniform
printing on the curved surface is obtained. Retinal vessels on
a curved surface are obtained by overlaying patterned
PDMS sheets on a curved surface, as shown in Fig. 5.
With this hydraulic transfer process, we can realize the
fine microchannel with size of ≃ 10 μm on a curved
surface, which is difficult to achieve with conventional
The details of fabrication are as follows:
1. Pattern SU-8 photoresist (Nippon Kayaku Co. Ltd,
Tokyo, Japan) on a silicon surface by laser
lithography. This pattern is used as a mold for the
microchannels and the size of the microchannels can be locally
controlled by adjusting the exposure conditions.
Fig. 5 Fabrication process for proposed retinal vessel model
2. Spincoat LOR (Nippon Kayaku Co. Ltd., Tokyo,
Japan) and PDMS (Silpot 184, Dow Corning Toray
Co. Ltd., Tokyo, Japan) onto the cured PDMS.
3. Push SU-8 mold ointo spin-coated PDMS and heat
the ensemble to 85 °C for 10 min with a hot plate.
4. Dissolve LOR with ethanol and remove PDMS sheet.
5. Transfer PDMS sheet to base structure by using
hydraulic transfer. The base structure is made by a
3D printer (EDEN250, Stratasys Ltd.). The diameter
of the base structure is 24 mm, which is the average
diameter of a human eye.
6. Transfer the PDMS sheet to the concave PDMS
made by 3D-printer mold. Prior to this step, treat
both bonding surfaces with O2 plasma for
surfaceactivated bonding of PDMS.
7. Remove base structure.
8. Pattern a connection channel at the bottom of the
curved PDMS surface. The mold for the connection
channel is fabricated by photolithography.
9. Punch holes into microchannel and connection
channel to connect external tubes.
10. For a cover layer, bond the thin PDMS sheet to the
curved surface. The polyvinyl alcohol (PVA) and
thin PDMS sheet are coated onto the base structure
by dip coating. The PVA is used to demold the thin
PDMS sheet from the base structure.
11. Dissolve PVA with hot water and remove base
12. Bond bottom glass to model to seal the connection
channel and connect the external tubes.
In this fabrication process, the 10-μm-sized
microchannel can be fabricated by using laser lithography (step
1 in Fig. 5). The patterning on a curved structure is done
by using hydraulic transfer (steps 5 and 6). Furthermore,
the thickness of the cover layer is controlled by changing
the dip-coating conditions (step 10). This means that the
wall thickness of the microchannels can be controlled
to best mimic the sensation of touching retinal vessels.
According to Ref. , the wall thickness of retinal
vessels ranges in humans from 10 to 20 μm. We tentatively
confirmed that this range can be covered by changing the
drawing speed of the dip-coating process. In this study,
we use a 20 μm cover layer.
According to our proposed fabrication process, the cross
section of the fabricated vessel model is square because
the cross-section of the patterned photoresist is square.
We have already fabricated the vessel model with
circular vessel cross sections by using a reflow process with
the patterned photoresist . However, this approach
requires additional processing steps, wihch increases the
cost of fabrication. Therefore, this approach is not favored
for commercial versions of this model. In addition, we
made preliminary evaluations of both the square- and
circular-cross-section microchannels. According to
qualitative evaluations of these two models by medical doctors,
no significant difference is apparent between the models
with vessels of different cross-sectional shape. We
therefore used vessels with square cross-sections in this study.
The fabricated retinal vessel model is shown in Fig. 6.
The channel was neither broken nor collapsed after the
hydraulic transfer, as shown in Fig. 6b and c. We varied
the width and height of the vessels from 75.0 to 119.1 μm
to mimic the size range of actual retinal vessels. Details of
the design values and the measured results for the three
typical parts of the samples are shown in Table 1. The
Fig. 6 Photographs of fabricated model: a overview, b cross-sectional view cut along line A-A’, and c enlarged image of cross-sectional view
Table 1 Measurements of fabricated model (N = 5)
aspect ratio of these vessels is approximately 1.0. In
addition, we evaluate the thickness of the cover-layer PDMS
sheet, which is related to sensation of touching a retinal
vessel. We measured the thickness at five points on a
sample and the average value of these five thicknesses is
19.3 ± 0.3 μm, which is close to the target value of 20 μm.
The standard deviation of the thickness is less than 2 %
of the target value. Thus, we conclude that the proposed
model can be fabricated with good reproducibility.
Next, we tested the circulation of liquid in the
microchannel by injecting a blue liquid into the
microchannel via the external tube connected to the model. The
injected liquid circulated through the channel without
leakage, as shown in Fig. 7 (Additional file 1).
Based on these results, we conclude that the proposed
retinal vessel model was successfully fabricated on a
concave surface. This fabrication method can thus be used to
fabricate microchannels on concave surfaces.
1. Approach target retinal vessel with micropipette.
2. Puncture target vessel with micropipette.
3. Inject thrombolytic drug via the micropipette and
hold micropipette in place for approximately 30 s.
4. Withdraw micropipette from retinal vessel. Additionally, we measured the vertical force applied to the model during this procedure by using a load cell placed underneath the model.
Photographs taken before and after puncturing (step
2) are shown in Fig. 8a and b, respectively. The
micropipettes successfully puncture the microchannel and inject
the liquid into the channel (Additional file 2). The
vertical force applied during the procedure is shown in Fig. 8c
and varies from approximately −150 to 180 mN. Here,
negative values indicate that the force is applied
downward towards the model (i.e., a pushing force). Similarly,
positive values indicate a pulling force. Thus this model
allows quantitative measurements of the force applied
during the simulation of a microcannulation procedure.
We propose herein a retinal vessel model and describe
how to fabricate the model. Further functionalization of
the proposed model is also discussed.
Simulating entire steps of microcannulation surgery
requires a whole-eye model. In this study, we focus on
simulating the retinal vessels at the posterior segment
of the eye. Our model can be used to simulate the
puncture and injection processes in microcannulation surgery.
However, other processes in an actual operation, such as
insertion of forceps into the eyeball, should also be
simulated. To do so would require a whole-eye model that can
mimic the structures and mechanical characteristics of
Fig. 7 Successive photographs of the circulation of liquid through
the microchannel: a start of circulation and b 10 s later. The black
arrows point to the air-liquid interface, whereas the blue dotted arrows
show the direction of flow
whole parts of the human eyeball. The fabrication of such
a complex 3D structure with the appropriate materials is
planned in future work.
Furthermore, we demonstrate the measurement of
applied force with the proposed model, as shown in
Fig. 8c. Integrating such sensing functions into a
mockup surgical simulator is of great use for quantitatively
evaluating medical techniques. Other surgical
procedures use thermal or electrical effects for treatments.
Simulating the associated sensing functions (e.g., thermal
or electrical sensors) is required to evaluate these
surgical procedures. Such highly-functionalized surgical
simulators will be reported in the near future.
Fig. 8 Results of microcannulation simulation: photographs of retinal
vessel model a before and b after puncture of retinal vessel by
micropipette. These photographs were acquired by using an eye-surgery
microscope. c Measured force applied during microcannulation
We propose herein a retinal vessel model fabricated on a
concave surface to simulate microcannulation. The
structure of the proposed model is very reproducible and can
be sterilized for use in actual operating rooms. The model
is fabricated by using laser lithography, PDMS molding,
and hydraulic transfer, and can create vessels as small
as 10 μm in size. Furthermore, we confirmed that
liquid can be circulated through the fabricated
microchannel. In addition, we simulate the puncture and injection
processes of microcannulation. We also measure the
applied force by using a force sensor placed underneath
the model. Such sensing is quite important to
quantitatively evaluate surgical skills or the performance of
medical equipment. The proposed retinal vessel model and the
associated sensing function strongly contribute to
evaluating medical techniques, which are vital to ensure
highquality and safe medical procedures.
Additional file 1: Circulation. Movie file of liquid circulation to
fabricated retinal vessel model (Fig. 7).
Additional file 2: Puncture. Movie file of simulation of puncture and
injection process with fabricatedretinal vessel model (Fig. 8).
All authors performed conception and design of the study. IK performed
collection of data, analysis and interpretation of data, TH and FA performed
drafting of the manuscript and all authors performed critical revision of the
manuscript. All authors read and approved the final manuscript.
This study was supported by Grant-in-Aid of the program Impulsing Paradigm
Change through Disruptive Technologies Program (ImPACT).
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