Flexible Microfabricated Parylene Multielectrode Arrays forRetinal Stimulation and Spinal Cord Field Modulation
Damien C. Rodger1,2, Wen Li1, Andy J. Fong1, Hossein Ameri2, Ellis Meng2, Joel W. Burdick1,Roland R. Roy3, V. Reggie Edgerton3, James D. Weiland2, Mark S. Humayun2 and Yu-Chong Tai1
1
California Institute of Technology, 1200 E. California Blvd., M/C 136-93, Pasadena, CA 91125, U.S.A.
Tel: +1-626-395-8477, Fax: +1-626-584-9104, E-mail: dcrodger@mems.caltech.edu
2
University of Southern California, Los Angeles, CA 90033, U.S.A.
3University of California, Los Angeles, Los Angeles, CA 90095, U.S.A.
ABSTRACTThe first flexible parylene-based multielectrode arrays (MEAs) designed for functional electrical stimulation (FES) in retinal
prostheses, and the extension of this technology toward enabling reflex-arc neuromodulation in cases of spinal cord damage ortransection, are presented. A single metal layer 16 × 16 retinal electrode array of 125 μm-diameter thin-film Ti/Pt electrodes and linesof 12 μm-pitch has been fabricated as a demonstration of this technology. To allow for even higher density arrays, a novel dual-layer
process has also been implemented that enables leads to pass under overlying electrodes without making electrical contact to them. A
biomimetic parylene-based electrode array consisting of 1024 electrodes of highly variable spacing, 60 of which have been connectedin this manner, has been fabricated according to this paradigm. A parylene-parylene annealing process has also been developed toincrease device longevity under accelerated-lifetime saline soak conditions. Surgical tests of novel anatomically-conformal
geometries that enable such parylene-based electrode systems to interact with their neuronal targets of interest while causing minimalmechanical damage to tissues or to the implants are also presented. The use of these flexible electrode arrays in spinal cord
stimulation experiments in animal models has proven their efficacy in stimulating neurons.
Keywords: BioMEMS, Dual-layer, Electrode array, Neural prosthesis, Parylene, Retinal prosthesis
1 INTRODUCTION
Prototypical hand-made retinal prostheses have shown great
promise, enabling subjects blind from such diseases as retinitis
pigmentosa and age-related macular degeneration to perceive
visual data [1]. The next-generation retinal prosthesis (Fig. 1),
however, requires a high-density flexible electrode array and ahigh lead-count cable to allow for high resolution vision. We aredeveloping
parylene-based
technologies
thatusemicrofabrication techniques to increase the electrode densities
by more than an order of magnitude over the state-of-the-art 16electrode implant being used in such studies. These technologies
include parylene-based electrode arrays and flexible cables,
radiofrequency (RF) coils for power and data transmission, andscalable interconnect packages for connecting prefabricatedapplication-specific integrated circuits (ASICs) and discretes
with the other system components [2]. We are adapting thesetechnologies to enable modulation of innate reflex-arcs throughFES from MEAs of a different geometry, with the aim offacilitating locomotion in cases of spinal cord damage. It has
been shown that such reflexes are preserved even in cases ofcomplete spinal cord transection [3]. Because our low-profile
flexible architectures obviate the positioning problems
associated with traditional wire-based electrode technologies,
these MEAs should minimize tissue damage while enabling
chronic electrical field modulation of multiple lumbosacral
segments through a single point of entry. The advantages of theuse of parylene C as the bulk-material for such neuroprostheses,
when compared with technologies based on the use of othermaterials such as polyimide [4] and silicon [5], include

Figure 1. Intraocular retinal prosthesis components.
parylene’s pinhole-free conformality, its low water
permeability, its United States Pharmacopeia (USP) Class VI
biocompatibility, and its flexibility and mechanical strength(Young’s modulus ~4 GPa).
In this work, we present electrode arrays fabricated using asingle metal-layer process. Building on this, a dual-layer process
has also been devised and implemented that enables theseelectrode arrays to overcome the wire-routing and electrodecrowding problems typically encountered in such high leadcount applications. Novel anatomically-conforming geometries
have also been developed and tested for both the intraocularretinal prosthesis and spinal cord applications, and demonstratethe implantability of these parylene-based technologies. Finally,
preliminary stimulation experiments have demonstrated thatthese electrode arrays are efficacious for neuronal stimulation.
2 FABRICATION
2.1 Single-layer process
The process flow for the fabrication of single-layer
multielectrode arrays is given elsewhere [6]. Briefly, ~8 μm of
parylene C is vapor-deposited on a standard silicon wafer (asacrificial photoresist precoating is optional). A subsequentthin-film metal deposition and liftoff forms the contacts,
conductive lines, and electrodes. A second layer of parylene C isthen deposited, and oxygen plasma is applied through aphotoresist mask to remove the parylene covering the electrodes
and contacts, as well as to form the overall array geometry. Theelectrodes are finally peeled from the wafer in an acetone orwater bath.
2.2 Dual-layer processDual-layer electrode arrays are fabricated as shown in Fig. 2.
Again, an optional sacrificial photoresist is spun on a standard
silicon wafer. A first parylene deposition on the entire wafer
forms the underside of the electrode array. A metal liftoff
pattern is exposed and developed into a photoresist mask using a10X reduction stepper. A subsequent 200 Å titanium and2000 Å platinum deposition and liftoff forms the first metal
layer, creating the traces that will underlie the metal electrodes.
A second parylene deposition (~1 μm) forms the insulation layer
between the two metal layers. 6 μm × 6 μm vias are patternedin this parylene layer using a photoresist mask in an oxygen
plasma reactive-ion etc. After stripping the photoresist, a second
liftoff pattern is exposed and developed in photoresist. Anothermetal deposition of 200 Å titanium and 2000 Å platinum andsubsequent photoresist strip forms the second layer of metal, andcoats the via sidewalls due to the slightly isotropic nature of thevia parylene etch [7]. The final parylene coating creates the top
insulation. To expose the electrodes and fabricate the overall
geometry, this parylene layer is then patterned with anotherphotoresist mask and reactive-ion etching in oxygen plasma.
Finally, the photoresist is stripped and the electrodes are peeledfrom the wafer in a water bath or released through removal of
the sacrificial photoresist in acetone.

Figure 2. Fabrication process for parylene-based dual-layer
multielectrode arrays.

2.3 Parylene-parylene annealing
These electrodes ideally undergo post-processing to preparethem for implantation or any electrochemical or acceleratedlifetime saline soak testing. It has been found that, in samples
that have not undergone post-processing, parylene-parylene
delamination can be observed sometimes in a matter of hours
under accelerated-lifetime conditions in 77°C saline. This
failure time depends on the processes performed on theunderlying layer of parylene before deposition of the overlying
layer. However, if the parylene stack is annealed in a vacuum
oven with nitrogen backfill at elevated temperatures for a shorttime (usually 200°C for 2 days) before soaking, a sample thatwould fail can be converted into one that remains stable underidentical conditions for more than one year. This paryleneparylene annealing process is now routinely performed on ourdevices prior to any further testing with excellent results.
3 BIOMIMETIC DESIGN
The dual-layer electrode fabrication process obviates the usual
concerns over wire routing and electrode crowding, because
more incoming traces can be on two separate layers, andbecause the first layer of traces can pass under overlying
electrodes. The traces would not have to be unreasonably
narrow (thus, high impedance) to route lines to all of theelectrodes in a 1024 electrode array. As an added benefit, it
facilitates electrode connections in arrays of multiple geometries
and with varying electrode-electrode spacing. In order todemonstrate this, an electrode array was fabricated in which theelectrode spacing was designed to more closely match (whencompared with arrays in the traditional grid arrangement) the
topography of the ganglion cells in the macula of the humanretina with respect to radial density [8] (Fig. 3).
Single layer retinal electrode arrays were also designed andfabricated to simulate the geometry of a fully-implantable
intraocular retinal prosthesis, comprising an RF coil region
designed for placement in the crystalline lens capsule, a flexible
cable that exits the posterior capsule, coursing through thevitreous cavity to the point of attachment of the electrode arraywith a retinal tack on the macula. These took into accountresults from previous surgical testing in which such problems as
cable length and traction of the RF coil region into the vitreous
cavity due to the point of attachment of the cable were noted. Inaddition to shortening the cable, capsular retaining-wings wereadded to the design so as to enable the flexible cable andelectrode array to bend away from the lens capsule while
retaining a tether to a stably-situated RF coil region. These
modifications were designed to enable the retinal prosthesis to
more closely conform to the anatomy of the eye while remaining

Figure 3. Biomimetic retinal microelectrode array layout.

securely anchored in place. Electrodes were added to these
surgical test structures to determine their resilience to theimplantation techniques. Each test structure contained a set of 4
electrodes, with each electrode connected by two traces tocontact pads in the RF coil region (two facilitate continuitytesting). The metallization of thin-film platinum in these test
devices was of comparable thickness to that envisioned for themetallization in the final device (~2000 Å to 3000 Å).
The electrode array designed for implantation and electricalfield modulation in spinal cord prostheses has been designed
according to similar biomimetics considerations (Fig. 4). The
small width of the array (1.2 mm) enables its insertion through asmall incision under the dura mater and threading along thespinal cord so as to be in close contact with multiple spinal
segments. Suture holes and tabs for manipulation with forceps
facilitate surgery and anchoring without excessive damage tothe traces or electrodes. The flexibility of the array is ultimately
its greatest attribute, in that it is bioconformal. The stiffness ofparylene is such that the material is neither too limp nor too
rigid when compared with other materials such as PDMS or
polyimide, respectively, while remaining robust under surgicalconditions.

Figure 4. Graphical depiction of bioconformal spinal cord MEA.
4 TESTING AND RESULTS
A fabricated single-layer electrode array, with 256 electrodes of
125 μm diameter in a traditional 5 mm-square 16 × 16 squaregrid arrangement with traces of 12 micron pitch is shown in Fig.
5a, and a scanning electron micrograph (SEM) depicting themorphology of the electrode and the parylene opening is shownin Fig. 5b. Energy dispersive spectroscopy (EDS) andelectrochemical tests have confirmed the lack of contaminationof the exposed platinum in these structures.

(a)

(a)

(b)

Figure 6. (a) Fabricated dual-layer electrode array and (b) SEM
micrograph detailing electrode geometry (note vias in center).

Figure 7. Magnified view of 6 μm × 6 μm via forming
connection between metal layers.
Fig. 6 shows a fabricated dual layer electrode array and ascanning electron micrograph of a typical electrode in this array.
A magnified view of a via making contact between theoverlying metal and the underlying trace in such an electrode isshown in Fig. 7, demonstrating the metal step coverage over theparylene sidewall. Electrical testing between the contacts
connected to each of the incoming traces has demonstrated atypical impedance in the range of 5 kΩ, including the two 8 μm
wide traces of 20 mm length as well as the via step junction.
The junction itself has been shown to have an impedance of lessthan 12.5 Ω. Additional testing has shown that traces are not
shorted to other electrodes under which they pass, and that
second-layer traces are not shorted to those underneath,indicating that there are no pinholes in the parylene insulation
layer. Electrochemical testing of these dual-layer electrodearrays is now underway.
A fabricated single-layer surgical test structure with embedded
traces is shown in Fig. 8. Pad-electrode-pad impedances weremeasured prior to surgical implantation of this device using theanticipated procedures in an ex vivo porcine eye and an in vivo(b)

Figure 5. (a) A 16 × 16 Ti/Pt electrode array and (b) SEM
micrograph detailing electrode geometry.

Figure 8. Surgical test structure for mechanical andelectrical characterization.

5 CONCLUSION(b)(a)
Figure 9. Surgical implantation under (a) anterior and(b) intravitreal illumination.

Parylene-based flexible MEAs for retinal and spinal cord
prostheses are being developed to solve such problems as
blindness from photoreceptor loss and locomotor dysfunction
due to spinal cord injury. Single-layer electrode arrays havebeen tested and implanted in animals to demonstrate that thesetechnologies are robust under surgical conditions andefficacious in stimulating neurons. A new dual-layer process has
been devised that significantly increases the possible electrodedensities possible in such arrays. It is of note that thistechnology is not restricted to two layers of metal. Indeed, it is a
simple task to add additional alternating layers of metal andparylene to enable even more complicated wire routing ifnecessary. In addition, this fabrication technology is not
restricted to the use of parylene, however the conformality anduniformity of the parylene deposition process facilitates thefabrication of such multilayer neural prosthetic devices.
ACKNOWLEDGEMENTS

(a)

(b)

Figure 10. Pad-electrode-pad circuit resistances before and after
surgical implantation in (a) porcine eye and (b) canine eye.
canine eye (surgical photographs under anterior (a) and intravitreal(b) illumination are shown in Fig. 9). After explantation, the line
impedances were measured and compared with those done prior.
The results graphed in Fig. 10 show that the pre-surgical coilelectrode-coil circuit impedances fell into two groups based on thephysical lengths of these circuits, the shorter having a meanimpedance of 135 Ω and the longer having a mean impedance of152 Ω. Post-surgical testing of the electrical characteristics of thecircuits revealed mean impedances of 136 Ω and 154 Ω for the
short and long circuits, respectively, with no lines having beenbroken during the surgical procedures. These results indicate thatthe embedded thin-film metal wires are robust under surgicalconditions.

Structural prototypes of parylene-based electrode arrays werefabricated implanted on the spinal cords of two mice withexcellent results. Based on these results, spinal cord electrodearrays were fabricated as shown in Fig. 11. One of theseelectrode arrays was implanted in contact with the spinal cord ofa mouse, and stimulation with simultaneous electromyogram
recordings demonstrated their efficacy in neuronal stimulation
over the testing period of several hours.

Figure 11. Fabricated spinal cord flexible electrode array.

This work was supported in part by the Engineering ResearchCenters Program of the National Science Foundation under NSF
Award Number EEC-0310723, and by a fellowship from theWhitaker Foundation (D.R.). The authors especially wish tothank Mr. Trevor Roper and other members of the Caltech
Micromachining Laboratory for their valuable assistance.
REFERENCES[1] M. S. Humayun, J. D. Weiland, G. Y. Fujii, R. Greenberg,
R. Williamson, J. Little, B. Mech, V. Cimmarusti, G. Van
Boemel, and G. Dagnelie, “Visual perception in a blind subject
with a chronic microelectronic retinal prosthesis,” Vision
Research, vol. 43, pp. 2573-2581, 2003.
[2] D. C. Rodger, J. D. Weiland, M. S. Humayun, and Y. C. Tai,
“Scalable flexible chip-level parylene package for high leadcount retinal prosthesis,” in Proc. Transducers, Seoul, SouthKorea, June 5-9, 2005, pp.1973-1976.
[3] A. J. Fong, L. L. Cai, C. K. Otoshi, D. J. Reinkensmeyer, J.
W. Burdick, R. R. Roy, and V. R. Edgerton, “Spinal cordtransected mice learn to step in response to quipazine treatment
and robotic training,” J. Neurosci., vol. 25, pp. 11738-11747,
2005.
[4] T. Stieglitz, W. Haberer, C. Lau, and M. Goertz, “Developmentof an inductively coupled epiretinal vision prosthesis,” in Proc.
IEEE-EMBS, San Francisco, CA, USA, Sept. 1-5, 2004, pp.
4178-4181.
[5] A. Hoogerwerf and K. Wise, “A three-dimensional
microelectrode array for chronic neural recording,” IEEE
Trans. Biomed. Eng., vol. 41, pp. 1136–1146, 1994.
[6] D. C. Rodger, W. Li, H. Ameri, A. Ray, J. D. Weiland, M.
S. Humayun, and Y. C. Tai, “Flexible parylene-based
microelectrode technology for intraocular retinal prostheses,” inProc. IEEE-NEMS 2006, Zhuhai, China, Jan. 18-21, 2006.
[7] E. Meng, and Y. C. Tai, “Parylene etching techniques for
microfluidics and bioMEMS,” in Proc. IEEE-MEMS,Miami, FL, USA, Jan. 30–Feb. 3, 2005, pp. 568-571.
[8] C. A. Curcio and K. A. Allen, “Topography of ganglioncells in human retina,” Journal of Comparative Neurology, vol.
300, pp. 5-25, 1990.