Proceedings - 19th International Conference - IEEE/EMBS Oct. 30 - Nov. 2, 1997 Chicago, IL.

USA

DEVELOPMENT OF FLEXIBLE STIMULATION DEVICES

FOR A RETINA IMPLANT SYSTEM
Thomas Stieglitz, Hansjoerg Beutel, Ralf Keller, Cornelia Blau, Joerg-Uwe Meyer
Fraunhofer Institute for Biomedical Engineering, Department of Sensor Systems / Microsystems, En-
sheimer Str. 48,D-66386 St. Ingbert, Germany
E-mail: [email protected]

ABSTRACT to the partners for acute and chronic implantation in animal

models.
Different research groups are focusing their work on the de-
velopment of a neural prostheses to aid patients suffering
from blindness. In some diseases (retinitis pigmentosa or
Keywords: retina implant, ganglion cell stimulation,
macula degeneration), degeneration of the photoreceptors
microelectrodes, biocompatibility
often leaves the ganglion cell layer and the central vision
system largely intact.
This paper outlines our approach of:interfacing the retina with
INTRODUCTION
flexible multielectrode structures for ganglion cell stimula-
tion. Results are given on the material selection for substrate A large number of patients suffer from retinal degenerative
materials and the design for flexible stimulation devices. By defects, especially retinitis pigmentosa (RP) and macular
means of cytotoxicity testing, in a first step of an evaluation degeneration. There is a progressive loss of rod and cone
procedure, the biocompatibility of different substrate and photoreceptors. However, the ganglion cell layer which forms
coating materials has been investigated. The methods were the optic nerve and subsequent parts of the visual system
sensitive to such a degree that even the influence of changes remain intact. In a recent study [l] it could be demonstrated
in process technology on the material was detected. Different that local electrical stimulation of the retinal ganglion cell
geometric test structures have been created that led to the layer in blind RP patients yielded useful, localized visual
design of flexible, light-weighted stimulation devices with sensations. These so-called "phosphenes" were seen as dots or
integrated cables. The devices were fabricated using mi- lines in defined locations in the visual space.
cromachining technology. We used polyimide as substrate
and insulation layers and platinum as electrode and intercon-
nect metallization layers. The first structures were distributed
microcontroller
for electronic receiver electrode selection
signal processing (energy and data) and encoding

:or-

(data and energy)

flexible stimulation
electrodes

Fig. I : Schematic illustration of the retina implant system for ganglion cell stimulation as envisioned in the German EPI-RET project.

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 Proceedings - 19th International Conference - IEEE/EMBS Oct. 30 - Nov. 2, 1997 Chicago, IL. USA

Several research groups are working on different approaches ported in detail elsewhere [ 1 I]. In the first design, several test
to by-pass the defective retina. One approach is an intracorti- structures without electrode metallization were produced to
cal stimulation array [2], which could also be applied in dis- evaluate the flexibility of different geometrical shapes (Fig 2
eases affecting the optic nerve or some higher parts of the & Fig. 3). The handling properties for an implantation were
central visual system. For direct stimulation of the retina two evaluated by a team of retina surgeons. These investigations
different implantation and stimulation locations are under resulted in a design of a stimulation device (Fig. 4, Table 1).
investigation: a subretinal location with photodiode arrays in The design comprises an active area with up to 24 concentric,
the region of the degenerated photoreceptor cells [3,4] and an bipolar electrodes, long integrated interconnects, and an area
epiretinal location for ganglion cell stimulation with for contacting microelectronic circuitry. The concentric elec-
“conventional” stimulation contacts. Components for the trodes were realized in a two metallization layer process.
ganglion cell stimulation implant are currently developed in Platinum was used for the thin-film electrodes, interconnects
several groups in the U.S. [5-71 and Germany [8,9]. and pads.
The idea of an intelligent retina implant was introduced as a The curvature of the device was adapted to the spherical
result from a feasibility study funded by the German research shaped bulbus in a temper step before implantation.
ministry BMBF [IO]. Our consortium consists of 14 groups
with approxomately 40 scientists comprising expertise in
microelectronics, optoelectronics, microsystem technology &
biomedical engineering, neural computation, biomaterial
science, retinal cell biology, vitreoretinal surgery, and visual
neurophysiology.
The whole system for a retina implant comprises several
functional units (Fig. I). The external part includes a high
speed camera to generate-the images. A retina encoder is used
to simulate the spatio-temporal properties of the different
layers of the retina. The encoder will process the signals from
the camera and generates stimulus patterns for the ganglion
cells. A telemetric unit for signal and data transmission is the
link to the implantable part of the system. Electrodes will be
spatio-temporally selected for current stimulation of the gan- Fig. 2: Test structures i n different sizes to investigate flexibility and
glion cells. handling: honeycomb, disk, ring, spiral (from left to right). Di-
ameter: 1.5 mm / 1.O mm / 2.0 mm (from top to bottom).

MATERIALS AND METHODS

The development of ultra-light weighted and flexible stimu-
lation devices to apply onto the retina requires a non toxic
material for the long-term use. Three different polyimides (PI
2556, PI 2566, PI 261 1, DuPont) were selected that are suit-
able for micromachining. The cytotoxicity of the materials
was determined as a first step in biocompatibility testing.
These in vitro investigations were performed with L929
(mouse fibroblasts) and Neuro2A (mouse neuroblastoma) cell
lines. Both cell lines have been shown to react highly sensi-
tive to a toxic stimulus. The testsystems were chosen accord-
ing to the purpose of the material: direct contact assays and
extract tests were performed according to the international
standard “Biological Evaluation of Medical Devices” (IS0 Fig. 3: Test structures with “interconnects” to investigate flexibility and
possible handling during implantation. Device diameter: 2.0 mm
10993) and USP-23. Cytotoxicity was determined by qualita- / 4.0 mm (top / bottom).
tive (cell morphology) and quantitative (integrity of the cell
membrane, DNA synthesis rate and metabolism of the cells)
means. RESULTS
The stimulation structures were fabricated applying mi- The in vitro screening of the three different polyimides
cromachining technology that enables the design of flexible, showed excellent biocompatibility for the materials PI 2556
ultra-light weighted devices. The process technology is re- and PI 2611 and good results for PI 2566. Apart from the

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 Proceedings - 19th International Conference - IEEE/EMBS Oct. 30 - Nov. 2, 1997 Chicago, IL. USA

general screening of substrate and coating materials, the of the medical partners. In chronic experiments, retina tacks
highly sensitive Neuro-2-A cells were used to perform quality were used to attach the electrode structure to the retina.
control of the different steps of the process technology. A
modification in an aluminum etch step in the fabrication
process resulted in an adverse cell morphology (Fig. 5) in
respect to the standard process characterized by intact cell
morphology (Fig. 6).

b
1

= iI
I
i Fig. 5: Altered morphology of a Neuro-2-A-cell culture when contacted
with polyimide PI 2566 that was exposed to aluminum etch solu-
i tion.
I
i
i, I

gi n
k, m
' P 0

Fig. 4: Drawing o f a flexible restina stimulation device.

number
a
n description
connection Dad width
II dimension
1500 um
Ib 11 conncction pad IcnEth 11 1500 um I
lixat ion
via liolc I'or lixation
interconnect length
interconnect width
Fig. 6: Morphology of an intact L-929-cell culture after contact with
diameter of device 4000 um polyimide PI 2556 (standard process technology).
400/1000/4000pm

distance between rings DISCUSSION

interelectrode distance 750 um
(1 thickness Multichannel devices for a retinal ganglion cell stimulation
were presented. We established the process technology for a
Table 1: Dimensions of the retina stimulation device.
multilayer device with two metallization layers. The elec-
trodes were designed quite large to overcome limitations of
The stimulation devices were fabricated in a version with platinum in charge injection. A smaller electrode will require
twelve and a version with 24 electrodes (Fig. 7). The com- a change to other electrode materials like iridium oxide or
plete structures weigh approximately 4 mg and are 15 pm fractal titanium nitride that have significant higher reversible
thick. Acute implantations were performed in rabbits at sites charge delivery capacities. In future designs the number of
electrodes will be increased up to 100. The interelectrode

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 Proceedings - 19th International Conference - IEEE/EMBS Oct. 30 - Nov. 2, 1997 Chicago, IL. USA

distance will be decreased resulting in the stimulation of only F. T. Hanibrecht. “Visual prostheses based on direct interfaces with
small populations of ganglion cells at higher spatial resolu- the visual system,” Neuroprostheses, G. S. Brindley and D. N. Rush-
ton Eds. London Philadelphia Sydney Tokyo Toronto: Bailliere Tin-
tion. dall, 1995, pp. 147-165.
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needed for induction of retinal and cortical potentials by stimulation
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ode arrays,” Invest. Uphthal. & Vis. Sci. vol. 37 (Suppl.), pp. 349,
1996.
1. F. Rizzo, S. Miller, T. Denison, T. Herndon, and J. L. Wyatt,
“Electrically-evoked potentials from stimulation of rabbit retina with
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“Development of a silicoii retinal implant: Microelectronic system for
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Sci. vol. 35 (Suppl.), pp. 1380, 1994.
Fig. 7: Retina stimulation device with 24 concentric stimulation elec-
M. V. Narayanan, J. F. Rizzo, D. J. Edell, and J. L. Wyatt,
trodes. Inner electrode diameter / area: 70 pm / 3850 pm2; ring
“Development of a Silicon Retinal Implant: Corical Evoked Poten-
electrode diameter / area: 200-230 pm / 10130 pm’. (SEM)
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CONCLUSION
R. Eckmiller, Retina implants with adaptive retina encoders Pro-
Flexible, ultra-light weighted devices were fabricated for ceedings of the RESNA Research Symposium, vol. pp. 21-24, 1996.
retinal ganglion cell stimulation. The electrode structure
M. Schwarz, B. J. Hosticka, M. Scholles, and R. Eckmiller, “Concept
adapts to the spherical shape of the eye without exerting pres- of a retina implant for ganglion cell stimulation applicable for pa-
sure on the retina. First chronic implants indicate that the tients suffering from retinitis pigmentosa,” Proc. of the Sih Vienna
electrodes are well suited for interfacing the retina. On-going International Workshop on FES, vol. pp. 413-416, 1995.
work will focus on the optimization of the electrodes with R. Eckmiller et al. Neurotechnologie-Report, Teil 1 & 2, BMFT
regard to the charge delivery capacity and to system integra- /BMBF, Bonn, 6. April 1994 / 3 1 . M k z 1995.
tion. T. Stieglitz, H. Beutel, J . 4 . Meyer, “A flexible, light-weighted,
multichannel sieve electrode with integrated cables for interfacing re-
generating peripheral nerves,” Sens. & Act., accepted paper, 1997.
ACKNOWLEDGMENT
The work presented here is supported by the German Minis-
try for Education, Science, Research, and Technology
(BMBF) and it is result of a team effort of the entire retina
implant consortium: (the three coordinaters are undelined)
B.Hosticka/Duisburg, D. JaegedDuisburg, W. Mokwa/ Duis-
burg, B. Wagner/ltzehoe, R. Eckmiller/Bonn, C. Mitter-
mayedAachen, M. EckmiIlerlDusseldorf, K. HeimandKoeln,
R. EffedEssen, H. Gerding/Muenster, L. Hesse/Marburg, P.
WiedemandLeipzig, R. Eckhorn/Marburg.
The authors especially would like to thank B. Kasemann and
S. Wien for performing the cytotoxicity testing on the process
materials and devices.

REFERENCES

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