Content uploaded by Vasiliki Giagka
Author content
All content in this area was uploaded by Vasiliki Giagka on Jul 19, 2023
Content may be subject to copyright.
Abstract— Ultrasound (US)-based neuromodulation has
recently emerged as a spatially selective yet non-invasive
alternative to conventional electrically-based neural interfaces.
However, the fundamental mechanisms of US neuromodulation
are not yet clarified. Thus, there is a need for in-vitro bimodal
investigation tools that allow us to compare the effect of US
versus electrically-induced neural activity in the vicinity of the
transducing element. To this end, we propose a MicroElectrode-
MicroTransducer Array (MEMTA), where a dense array of
electrodes is co-fabricated on top of a similarly dense array of
US transducers.
In this paper, we test the proof of concept for such co-fabrication
using a non-monolithic approach, where, at its most challenging
scenario, desired topologies require electrodes to be formed
directly on top of fragile piezoelectric micromachined
ultrasound transducer (PMUTs) membranes. On top of the
PMUTs, a thin-film microelectrode array was developed
utilizing microfabrication processes, including metal sputtering,
lithography, etching and soft encapsulation. The samples were
analysed through focused ion beam–scanning electron
microscopy (FIB-SEM), and the results have shown that damage
to the membranes does not occur during any of the process steps.
This paper proves that the non-monolithic development of a
miniaturised bimodal neuroscientific investigation tool can be
achieved, thus, opening up a series of possibilities for further
understanding and investigation of the nervous system.
I. INTRODUCTION
Bioelectronic medicine aims to develop locally specific
and reversible therapies based on modulating the electrical,
rather than the chemical component, of neural signalling.
Neural interfaces that use electricity as a means of stimulation
can already achieve increased precision [1] [2]. However, they
tend to become more invasive with the increase in spatial
selectivity [3]. Ultrasound (US) has recently emerged as
another promising spatially-selective neuromodulation
modality [4] [5] [6], which comes with the advantage that it
can be applied non-invasively. However, the fundamental
mechanisms of US neuromodulation have yet to be fully
elucidated. Moreover, having a fair comparison between the
effects of US-induced and electrically-induced
neuromodulation is currently impossible due to the lack of
suitable neuroscientific tools. While the induced activity can
be recorded via calcium imaging in an in-vitro setup, a high-
resolution tool that allows us to deliver both neuromodulation
modalities individually, at the exact location is still needed.
* Research supported by the Moore4Medical project funded by the
ECSEL Joint Undertaking under grant number H2020-ECSEL-2019-IA-
876190.
A.I. Velea and V. Giagka are with the Bioelectronics Section, Dept. of
Microelectronics, Faculty of Electrical Engineering, Mathematics and
Therefore, this paper aims to showcase the possibility of
integrating/co-fabricating a high-density microelectrode array
(MEA) on an existing array of micromachined ultrasound
transducers (MUTs) in a non-monolithic approach. A
microelectrode-microtransducer array (MEMTA) could serve
as a bimodal investigation tool to elucidate the fundamental
mechanisms involved in neuromodulation and enable further
neuroscientific discoveries. To demonstrate the feasibility of
this approach, this paper has investigated the fabrication of
thin-film metal electrodes directly on the surface of the MUTs,
while ensuring that damage to the membranes does not occur
during the process. A schematic representation of the proposed
concept is shown in figure 1.
II. METHODS
A. Ultrasound transducer array
Arrays of miniaturised US transducers can be developed
by dicing films of piezoelectric material (usually PZT) [7].
Alternatively, micromachining techniques can be used to
create capacitive or piezoelectric ultrasound transducers
(CMUTs and PMUTs, respectively). In this case, a thin
membrane suspended above a vacuum cavity vibrates in a
flexural mode to produce or receive acoustic waves [8], while
a pair of top and bottom electrodes is responsible for the
transduction between the electric and acoustic domain. The
latter technique lends itself to easier and scalable fabrication
Computer Science, Delft University of Technology, the Netherlands
(Corresponding author e-mail: A.Velea-1@tudelft.nl).
A.I. Velea, J. Wilson, A. Gollhardt and V. Giagka are with the Fraunhofer
Institute for Reliability and Microintegration IZM.
C. Karuthedath and A. S. Thanniyil are with the VTT Technical Research
Centre of Finland Ltd.
Non-monolithic fabrication of thin-film microelectrode arrays on
PMUT transducers as a bimodal neuroscientific investigation tool*
Andrada I. Velea, Student Member, IEEE, Joshua Wilson, Astrid Gollhardt, Cyril B. Karuthedath,
Abhilash S. Thanniyil, and Vasiliki Giagka, Senior Member, IEEE
Figure 1. Illustration of the proposed microfabricated bimodal
neuroscientific tool.
of miniaturised transducers and is fully compatible with
microfabrication processes; hence it has been the choice for
the transducers presented in this work. Specifically, 2x2 cm
silicon (Si) dies, having a densely packed array of cells (1296
cells with a 120 µm pitch), which could be addressed
individually or in smaller clusters, provided by VTT,
Technical Research Centre Finland Ltd., have been used for
the investigations presented in this paper. The structure and
material stack of each PMUT is shown in figure 2. The
substrate comprises a Si layer with vacuum cavities. On top, a
silicon dioxide (SiO2) passivation layer is present. The
vibrating element (i.e., aluminium nitride (AlN) layer) is
sandwiched between a bottom molybdenum (Mo) and a top
aluminium (Al) electrode. Finally, a silicon nitride (SiN) layer
acts as passivation for the entire array.
B. Microelectrode array
The MEAs used in this study (figure 3) comprise 28
electrodes placed in the centre of the PMUT array with an
opening of 40 µm in diameter and a pitch of 120 µm. Smaller
pitches that could lead to a denser MEA are also possible, but
demonstrating this was out of the scope for this work.
Regarding the materials used, soft polymers (i.e.,
thermoplastic polyurethane (TPU)) were chosen as a substrate
and encapsulation, as well as a stack of thin-film metals
(titanium (Ti) and gold (Au)) as conductors. Ti is used here as
a seed layer to improve the adhesion between the soft polymer-
based substrate and Au. On the other hand, Au, which will later
be exposed and in contact with the in-vitro medium, has been
chosen due to its known biocompatibility characteristics.
Although the metal layers can be directly deposited on the
existing passivation [9], we chose to deposit an additional
layer of TPU to allow the electrodes and pads to extend beyond
the rigid PMUT array, enabling integration of MEMTA into
flexible devices, for future applications. Due to their
thermoplastic nature, the TPU sheets (Platilon 4201AU,
Covestro AG, Germany) will melt and reshape under elevated
temperatures, thus ensuring that no interface is present
between two individual layers [10] [11].
C. Fabrication of test structures
A schematic representation of the microfabrication
process flow used in this work is shown in figure 4. First, a
25 µm thick layer of TPU was laminated on top of the PMUT
array, using a vacuum applicator (VA 7124-HP7 from
Dynachem Automatic Lamination Technologies, Italy) at
160 °C and 6 bar. Next, 50 nm Ti and 50 nm Au were
sputtered (500 W power for Ti and 250 W power for Au at
5x10-3 mbar) on top. Before sputtering, an argon-based (Ar)
RF surface pre-treatment was performed for 5 minutes using
50 W of power to further increase the adhesion between the
sputtered layer and TPU. Furthermore, an Ar-based surface
post-treatment using the same parameters as for the pre-
treatment was employed to improve the adhesion between the
sputtered layer and the photoresist used during the
lithography step. The lithography process uses a 10 µm thick
dry negative photoresist film (RY5110, Resonac, Japan) as a
mask, laminated at 67 °C and 6 bar, exposed using a
micromirror digital imaging system (MDI) (Schmoll
Maschinen GmbH, Germany) and developed in sodium
carbonate (Na2CO3) in a 0.9% concentration. Later, the
sputtered metal layer was wet-etched, manually, in a beaker,
in a two-step process, using gold stripper 645 from Schloetter
for Au, at room temperature and 95% Meltex LTF E53 mixed
with 5% hydrogen peroxide (H2O2) with a concentration of
30% at 50 °C for Ti. After the removal of the photoresist mask
using a mixture of 2-aminoethanol (C2H7NO) and potassium
hydroxide (KOH) with a concentration of 10-12% at 50 °C, a
second TPU layer was laminated at 160 °C and 6 bar.
Figure 2. Schematic representation of one PMUT cell of the array used
for the investigations. The vibrating membrane comprising top Al and
bottom Mo electrodes as well as the piezoelectric material (AlN) are
suspended above the vacuum cavity developed within the Si die.
Figure 3. Mask design of the microelectrode array developed on the
surface of the PMUTs. In grey, the location of the membranes on the
PMUT array. In yellow, the metal layer and in pink, the exposed
electrodes.
Figure 4. Schematic representation of the fabrication process.
Figure 5. Sample after lithography. The dark grey layer
represents the patterned photoresist on top of the metal layer.
Finally, the electrode contacts were exposed by dry
etching of the TPU layer using a March PCB 800 system
(from Nordson Electronics Solutions, USA). To this end, a
second lithography step was required to define the areas to be
etched. Instead of a metal hard mask, a thicker photoresist
layer (25 µm thick dry resist film RD1225, Resonac, Japan)
was laminated at 85 °C and 6 bar. The TPU dry etching
process parameters were as follows: 60 °C temperature, 240
mTorr pressure and 4 kW power, using a mixture of several
gases: 80% oxygen (O2), 10% carbon tetrafluoride (CF4) and
10% Ar, for 2 hours.
D. Analysis methods
After each process step, focused ion beam – scanning
electron microscopy (FIB-SEM) was employed to analyse the
samples and identify potential failures during fabrication. All
FIB cuts were made at locations where membranes only or
membranes and electrodes were present.
III. RESULTS AND DISCUSSION
For the proposed device, the focus was on developing a
MEA on top of an existent PMUT array. To this end, an array
of 28 Ti/Au electrodes was designed and fabricated on a TPU
layer previously laminated on the PMUT array. Figure 5
shows the microelectrode array after completion of the
lithography steps. To preserve the functionality of the final
device, it is crucial to ensure the integrity of each structure but
more importantly, of the membrane, after each
microfabrication process step. Figure 6a illustrates the
structure and layer stack of a bare PMUT array as received
from the manufacturer. This die was used as a reference during
the investigations. Figure 6b shows the device after the first
fabrication step (i.e., TPU lamination). It can be seen that the
structure of the membranes does not present any defects,
although the arrays were subjected to elevated temperature
(160 °C) and pressure during this step. Important to note are
the particles within the TPU layer.
a) FIB-SEM control sample.
b) Sample after 1st TPU lamination.
c) Sample after metal sputtering.
d) Sample after lithography.
e) Sample after metal etching and resist removal.
f) Sample after 2nd TPU lamination and dry etching.
Figure 6. FIB-SEM analysis of the manufactured samples after each fabrication process step.
These are not a consequence of contamination during
fabrication, as all process steps were performed in a clean
environment. However, the exact nature of these particles is
unknown, and the material supplier could not provide further
details. Another aspect related to the creation of the FIB cuts
is the material redeposition in some areas across the sample.
Nevertheless, this does not have a negative impact on the
overall results. Figure 6c shows the structure of the
membranes after sputtering the stack of biocompatible metals
(Ti and Au) on top of TPU. As observed, the membrane
remains stable after this second step. The layer thicknesses are
as expected (~50 nm of Ti and ~50 nm of Au), with a slight
variation, within the accepted tolerance ranges. The two
platinum (Pt) layers present above the sputtered layer are not
part of the final device; however, they provide additional
protection for the inspected layer during the ion beam
bombardment used for the analysis. It can be noted that the
surface of the TPU layer is not perfectly flat. This is because
the vacuum applicator used for lamination requires the use of
anti-adhesive mats on its top and bottom plates. When pressed
against the sample, the non-uniformities present on the surface
of these mats are also transferred to the TPU layer. Figure 6d
illustrates the layer stack and structure of the sample after the
lithography process. Despite the additional layers having
different properties, thicknesses and stiffness coefficients, the
membrane of the PMUT array is undamaged. Figure 6e shows
the sample after metal etching and photoresist removal. The
location of the metal electrodes and the alignment to the
underlying membrane can be clearly observed. Important to
note is the presence of metal residues due to the manual nature
of the etching process. At this point, a short over-etching step
is recommended to ensure that the sample is free of residues,
which, if present in large amounts, can even lead to unwanted
short circuits between the electrodes or tracks. Finally,
figure 6f shows the complete structure of the sample,
including the final TPU encapsulation and exposure of the
electrodes. Since the metal layer is no thicker than 100 nm, a
laser patterning technique [12], which would have reduced the
number of processing steps, could not be employed. Instead,
dry etching of TPU was chosen for this step. The thick
photoresist layer used here as a mask was also partly consumed
during the process, and as observed in figure 6f, some residues
are present in the opened area. For this study, the aim was to
investigate the effect each critical fabrication step has on the
integrity of the membranes, and as shown, no negative results
were recorded. Therefore, optimising the final TPU etching
step will be considered in the future. This would require, first,
the use of a metal hard mask instead of a photoresist layer.
Having a correct choice of materials will ensure that the
masking layer will not be consumed during the process, and
thus, no residues should be redeposited in the opened areas.
Moreover, the etching time for such diameters has to be
increased to remove the final, 1 µm-thick TPU from the
surface of the metal electrodes.
IV. CONCLUSION
This paper presents feasibility proof for the development of
a miniaturized multimodal investigation tool comprising both
PMUTs and MEAs. In particular, we have demonstrated that
soft MEAs, can be developed, in a non-monolithic approach,
on the surface of pre-existing PMUTs, without negatively
affecting the integrity of the membranes throughout a variety
of process steps, including, sputtering of metals, wet etching
and polymer lamination under high temperature and pressure.
This work could serve as a stepping stone in integrating
several neuromodulation and recording modalities on the
same miniaturized in-vitro investigation tool to enable a better
understanding of the various neuromodulation mechanisms.
ACKNOWLEDGMENT
We acknowledge our colleagues Sven Schmidt and
Friedrich Leonhard Schein, from the Fraunhofer Institute for
Reliability and Microintegration IZM, Berlin, Germany for
their support offered throughout the project.
REFERENCES
[1]
V. Giagka and W. A. Serdijn, “Realizing flexible bioelectronic
medicines for accessing the peripheral nerves – technology
considerations,” Bioelectron. Med., vol. 4, no. 8, pp. 1-10, June 2018,
doi: https://doi.org/10.1186/s42234-018-0010-y.
[2]
J. Dragas et al., “In Vitro Multi-Functional Microelectrode Array
Featuring 59 760 Electrodes, 2048 Electrophysiology Channels,
Stimulation, Impedance Measurement, and Neurotransmitter
Detection Channels,” IEEE JSSC, vol. 52, no. 6, pp. 1576-1590, June
2017, doi: 10.1109/JSSC.2017.2686580.
[3]
A. Branner, R. B. Stein, E. Fernandez, Y. Aoyagi and R. A. Normann,
“Long-term stimulation and recording with a penetrating
microelectrode array in cat sciatic nerve,” IEEE TBME, vol. 51, no. 1,
pp. 146-157, January 2004, doi: 10.1109/TBME.2003.820321.
[4]
M. E. Downs, S. A. Lee, G. Yang, S. Kim, Q. Wang and E. E.
Konofagou, “Non-invasive peripheral nerve stimulation via focused
ultrasound in vivo,” Phys. Med. Biol., vol. 63, no. 3, January 2018, doi:
10.1088/1361-6560/aa9fc2.
[5]
V. Cotero et al., “Noninvasive sub-organ ultrasound stimulation for
targeted neuromodulation,” Nat. Commun., vol. 10, no. 952, March
2019, doi: https://doi.org/10.1038/s41467-019-08750-9.
[6]
S. Kawasaki et al., “Pressure measurement of geometrically curved
ultrasound transducer array for spatially specific stimulation of the
vagus nerve,” in 2019 9th Int. IEEE Conf. NER, San Francisco, CA,
USA, 2019, doi: 10.1109/NER.2019.8717064.
[7]
T. Costa, C. Shi, K. Tien, J. Elloian, F. A. Cardoso and K. L. Shepard,
“An Integrated 2D Ultrasound Phased Array Transmitter in CMOS
With Pixel Pitch-Matched Beamforming,” IEEE TBioCAS, vol. 15, no.
4, pp. 731-742, August 2021, doi: 10.1109/TBCAS.2021.3096722.
[8]
Position II Consortium, “White paper discussing different technology
variants in relation to the application matrix,” ECSEL 2017-3-783132
POSITION II project.
[9]
K. Nanbakhsh, R. Ritasalo, W. A. Serdijn and V. Giagka, “Long-term
Encapsulation of Platinum Metallization Using a HfO2 ALD - PDMS
Bilayer for Non-hermetic Active Implants,” in 2020 70th Int. IEEE
Conf. ECTC, Orlando, FL, USA, 2020, doi:
10.1109/ECTC32862.2020.00081.
[10]
Y. S. Choi et al., “Stretchable, dynamic covalent polymers for soft,
long-lived bioresorbable electronic stimulators designed to facilitate
neuromuscular regeneration,” Nat. Commun., vol. 11, no. 5990,
November 2020, doi: https://doi.org/10.1038/s41467-020-19660-6.
[11]
A. Pak et al., “Thermoplastic polyurethane as a base material for
flexible neural interfaces,” in preparation.
[12]
A. I. Velea et al., “UV and IR Laser-Patterning for High-Density Thin-
Film Neural Interfaces,” in 2021 23rd Int. IEEE Conf. EMPC,
Gothenburg, Sweden, 2021, doi:
10.23919/EMPC53418.2021.9584962.