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@INPROCEEDINGS{RincnMontes:865223,
author = {Rincón Montes, Viviana and Srikantharajah, Kagithiri and
Kireev, Dmitry and Lange, Jaqueline and Offenhäusser,
Andreas},
title = {{F}rom stiff silicon to compliant retinal and cortical
multisite penetrating implants},
volume = {12},
issn = {1662-5102},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {FZJ-2019-04757},
pages = {0},
year = {2018},
abstract = {Motivation: For years, silicon has been successfully used
as the standard substrate material for the fabrication of
penetrating neural probes that perform electrical recording
as well as stimulation of single or multiple neuronal cells
in vivo. Nevertheless, the mechanical mismatch between the
stiff silicon and the surrounding soft tissue enhances acute
inflammatory responses [1] and hampers the long-term
stability and performance of such implants due to glial
scarring as a consequence of foreign body responses [2].
With the aim to fabricate more compliant neural probes, the
flexibility and softness of different polymer materials are
considered in this work for the optimization of the design
and fabrication of compliant retinal and cortical multisite
penetrating microelectrode arrays (MEAs). Furthermore, the
insertion of the proposed flexible systems is assessed
theoretically and tested experimentally for both retina and
brain tissues. In this work, we show the possibility to
perform electrical recording and stimulation with multisite
penetrating MEAs from both: thick brain tissue and thin
retina.Materials and Methods: Flexible substrate materials,
such as polyimide (Pi), parylene-C (Pa-C), and
polydimethylsiloxane (PDMS) are used for the fabrication of
compliant neural probes. The thickness (3-10 µm), the width
(50-100 µm), and the length (140-1000 µm) of a multi-shank
design were optimized in order to increase the theoretical
buckling force threshold for short/medium and long
penetrating shanks. Flexible structures with the
aforementioned thicknesses are compared with Si-based
structures through insertion tests in phantom neural
tissues, which are made out of PDMS mixed at different
polymer/curing agent ratios to achieve a Young’s modulus
akin to brain and retina (10kPa and 23kPa respectively).
Following the established designs, photolithography and
reactive-ion etching (RIE) techniques are used for the
microfabrication of such flexible devices. In addition, to
further increase the flexibility of the compliant probes,
conductive polymers and stretchable conductive layers with
serpentine and mesh designs are tested. Furthermore, the
feasibility to perform electrical recording and stimulation
is first tested with silicon based probes in light-adapted
wildtype retina in vitro.Results: Optimization of
cross-sectional dimensions show a higher buckling force
threshold for lower aspect ratio designs (e.g. 140 µm long
and 100 µm wide). Likewise, the calculation of buckling
force threshold for the different materials show that a
thickness of 6-10 µm should withstand the insertion of
silicon, Pi, and Pa-C probes when applying a tethering force
of 1mN, as is the case for brain tissue [1, 2]. In contrast,
PDMS would require a minimal thickness of approximately 70
µm. The theoretical calculations are also confirmed
experimentally with the probes penetration into phantom and
real tissue. Moreover, the use of penetrating MEAs and
recording inside the thin retinal tissue is proved to be
feasible. Discussion and Conclusion: The development of
penetrating and at the same time compliant neural probes
requires a trade-off between design considerations (length,
width, and thickness) and the mechanical properties of the
materials to be used during fabrication. On one hand,
flexible materials in an optimized cross-sectional design
might be used, however these are constrained to the
necessary length and maximum accepted thickness of the
implant to fulfill the requirements of the target
application. For example, while retinal applications demand
short shafts, long ones are required for brain. On the other
hand, the use of soft materials like PDMS is limited in
their use because their high softness drags out its handling
during fabrication and usage. Although an increase in
thickness might overcome some processing difficulties, the
required thickness for it might generate even higher trauma
than when using a stiff material, since a higher amount of
tissue is displaced during insertion. Hence, when working
with flexible and ultrathin implants, a proper strategy to
insert such systems into the tissue must be developed. Even
though different stiff and biodegradable shuttle solutions
have been proposed in the literature [1, 2], wafer scale
processes compatible with MEMS technology are still a
challenge. Therefore, in this work, further fabrication
steps comprising the integration of dry patterning and
lift-off techniques, as well as micro-molding, and
bio-degradable polymers are investigated for the development
of neural probes with built-in insertion shuttles.},
month = {Jul},
date = {2018-07-04},
organization = {11th Int. Meeting on Substrate
Integrated Microelectrode Arrays,
Reutlingen (Germany), 4 Jul 2018 - 6
Jul 2018},
cin = {ICS-8},
ddc = {610},
cid = {I:(DE-Juel1)ICS-8-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)8},
doi = {10.3389/conf.fncel.2018.38.00072},
url = {https://juser.fz-juelich.de/record/865223},
}