6th Annual International IEEE EMBS Conference on Neural Engineering
San Diego, California, 6 - 8 November, 2013

Perforated 2×2 Parylene Sheath Electrode Array for Chronic
Intracortical Recording*Seth A. Hara, Student Member, IEEE, Brian J. Kim, Jonathan T.W. Kuo, Curtis D. Lee, Christian A.
Gutierrez, Member, IEEE, Tuan Hoang, Victor Pikov, and Ellis Meng, Senior Member, IEEE

Abstract² We present the development of a perforated 2×2Parylene sheath electrode array (PSEA). Parylene C is surface
micromachined to create conical sheath structures withelectrode sites on the interior and exterior. Individual probes
can be configured into a 2×2 array. Building upon previous
designs, the sheath geometry was redesigned to have sharper
taper and incorporate perforations in order to minimize
insertion trauma and facilitate cell-cell signaling, respectively,
with the aim of improving long-term recording reliability.
Bioactive coatings were applied to the PSEA to encourage
dendritic growth and control the immune response. Benchtop
electrochemical results confirmed that electrode sites possess
appropriate impedance values for neural recording. A custommade insertion shuttle was fashioned to deliver the PSEA to thetarget location in the cortical tissue and then retract, leaving
only the flexible PSEA in the tissue. This system successfully
implanted multiple PSEAs into the rat M1 motor cortex and a 6month in vivo study is currently underway.
I. INTRODUCTION
Chronic intracortical recording continues to be achallenge as current probe technologies experience theattenuation or loss of neural signaling over time. The causesof these failures can be attributed both to abiotic issues,
such as compromised insulation, corrosion, or breakage, aswell as biotic responses, including the formation of a glial
sheath, activation of microglia, and neurodegeneration in theregion surrounding the probe. These biotic responses havebeen attributed to insertion trauma, the chronic presence of aforeign body, and the mechanical mismatch between theprobe and brain tissue [1-3].

conical polymer sheath with eight thin film Pt electrodesites, four on the interior of the sheath and four on the lateralexterior. Like the neurotrophic electrode, it utilizes
neurotrophic factors and anti-inflammatory coatings toencourage dendritic growth towards the electrode sites andmanage the immune response, respectively. Fabricated from
ORZ <RXQJ¶V PRGXOXV Parylene C polymer [5], however, it
more closely matches the mechanical properties of neuraltissue than the glass cone of the neurotrophic electrode orconventional metal and silicon neural probes.
We previously reported in detail on the fabrication of thePSE [6] as well as preliminary data demonstrating the use ofthis technology to record neuronal activity in vivo [7]. In thiswork, we present the use of our Parylene C sheath neuralprobe technology to develop a novel perforated 2×2 PSEA.
Each probe in the PSEA has eight electrodes for a total of 32
electrode sites. Utilizing lessons learned in a previous 28day in vivo study with un-perforated probes, the sheath tipsof the PSEA were redesigned with a sharp taper to minimize
insertion trauma as well as perforated throughout the sheathto promote cell-cell signaling and waste/nutrient exchange
for a reduced immune response and improved signal fidelity.

The Parylene sheath electrode (PSE) was designed toaddress this biological response in three ways: (1) use of athree-dimensional (3D) geometry that allows for tissue
growth into the open-lumen, thereby securing the probe inthe tissue, (2) improved mechanical matching to tissue, and(3) bioactive coatings to manage the immune response andencourage dendritic growth. This approach is similar to thatof the neurotrophic electrode [4]. Instead of using a rigid
glass sheath to house wire electrodes, the PSE consists of a
* This work was sponsored by the Defense Advanced Research Projects
Agency (DARPA) MTO under the auspices of Dr. Jack Judy through theSpace and Naval Warfare Systems Center, Pacific Grant/Contract No.
N66001-11-1-4207.
S. A. Hara, B.J. Kim, J.T.W. Kuo, C. Lee, T. Hoang, and E. Meng arewith the Department of Biomedical Engineering at the University ofSouthern California, Los Angeles, CA 90089 USA (corresponding author:213-821-3949; e-mail: ellis.meng@usc.edu).
C. A. Gutierrez is an independent engineering consultant in Los Angeles,
CA 90089.
V. Pikov is with the Huntington Medical Research Institutes (HMRI),
Pasadena, CA 91105.

978-1-4673-1969-0/13/$31.00 ©2013 IEEEFigure 1. Optical micrograph of the fully packaged 2×2 Parylene sheath
electrode array. Scale bar = 500 µm.

Benchtop electrochemical testing was conducted toevaluate electrode functionality and a coating process wasdeveloped to completely cover the hydrophobic Parylene C
sheath surfaces with the bioactive coatings.
A custom-made insertion shuttle was developed todeliver the flexible PSEA to the desired depth in the corticaltissue. The shuttle is then retracted from the tissue, leaving
the PSEA in place. This technique was first demonstrated inan agarose brain model and was subsequently successfully
implemented in the rat M1 motor cortex to enable a chronic
in vivo study.

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II. MATERIALS AND METHODS
A. Probe Design
Parylene C, a USP Class VI polymer was selected as thesubstrate and insulating material. Parylene C can be surface
micromachined, allowing for repeatable, high-throughput
batch fabrication of the PSEA. Electrode sites and leads arepatterned from thin film Pt, a biocompatible, inert metal
often used in neural interfaces [8].
A previous in vivo study indicated that the use of anarrow, sharply-tapered sheath geometry is preferred as it
minimizes damage to the surrounding tissue. Using this data,
we designed a sheath with a taper from 50 to 300 µm.
Additionally, in an effort to minimize inhibition of cell-cellchemical signaling, perforations were etched through boththe top and bottom of the sheath structure. PSEAs werefabricated in 1×2 arrays on wafer with individual sheaths
positioned 1 mm apart. Two 1×2 arrays are packaged backto-back to create a 2×2 array with the four sheaths correctly
spaced to target the rat M1 motor cortex.

Figure 3. Abbreviated fabrication process for the perforated PSEA. Note:
only the final outline of a single sheath is depicted for clarity.

Figure 4. Photographs (top row) and illustrations (bottom row) showing thethermoforming process used to obtain the 3D sheath. Scale bar = 100 µm.

Figure 2. Optical micrograph of the tips of a 1×2 perforated Parylene
sheath electrode array. Scale bar = 200 µm.

B. Fabrication and Thermoforming
A comprehensive description of the fabrication of thePSE was previously presented [6]. Briefly, thin film Pt
electrodes and leads were e-beam evaporated and patterned
via a lift-off process onto a Parylene C substrate on top of a
Si carrier wafer (Fig. 3a). Additional Parylene C wasdeposited via vapor deposition to insulate the leads, followedby an oxygen plasma etch to expose electrode sites and etchperforations through the substrate (Fig. 3b). A third layer ofParylene C formed a trapezoidal microchannel through theuse of a sacrificial photoresist mold (Fig. 3c). Electrodesites, perforations, and both sides of the microchannel wereetched open with oxygen plasma (Fig. 3d). Finally, the final
outline of the arrays was etched out, the arrays were released
from the wafer, and the sacrificial photoresist was removed
through an acetone soak (Fig. 3e). The probe was thenthermoformed to its final shape using a microwire mold(Fig. 3f).
To create the 3D sheath structure from the initially flat
surface micromachined channel (Fig. 4a), a custom-tapered
microwire mold was inserted into each microchannel tomechanically open the sheath (Fig. 4b). With the microwire
mold in place, the entire array was annealed at 200°C for 48
hrs. The microwires were then removed and the sheaths
maintain their 3D shape (Fig. 4c).

C. Packaging
A zero-insertion-force (ZIF) socket was used to reversiblyattach the PSEA without the use of wirebonding, conductive
epoxy, or soldering to a flexible PCB used to interface withthe recording system. To create the 2×2 array, two 1×2arrays were each inserted into back-to-back ZIF sockets on
the same double-sided PCB (Fig. 5).

Figure 5. Side view of the packaged PSEA, showing the back-to-backplacement of ZIF sockets. Scale bar = 1 mm.

D. Electrochemical Testing
Cyclic voltammetry (CV) was performed prior to testing
to remove contaminants from the electrode surface(electrochemical cleaning) [9]. CVs were conducted in0.05M H2SO4 from -0.2V to 1.2V at 250 mV/s for 30 cycles.

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Electrochemical
impedance
spectroscopy(EIS)
measurements were taken in 1× PBS with a 10 mV
perturbation signal in a frequency range of 1-100,000 Hz.
An Ag/AgCl reference electrode and 1 cm2 Pt plate counterelectrode were used for both tests.
E. Insertion ShuttleAlthough the flexible substrate of the PSEA is desirable
in vivo, the lack of rigidity inhibits the insertion of the array
into the cortical tissue. Therefore, a custom-made insertion
shuttle using stiff metal microwires was fashioned to provide
the necessary temporary stiffness to deliver the PSEA to thedesired depth in the cortex. The acrylic shuttle has laseretched grooves to position four tungsten microwires (300µm diameter) 1 mm apart laterally as well as in depth. Toaffix the array to the insertion shuttle, polyethylene glycol(PEG) was used as a biodegradable adhesive to mount thesheaths to the sides of the microwires and also to provide
some strain relief by attaching the flexible PCB to theacrylic shuttle. This method along with the physicalarrangement of the wires allows the four probes of the array
to be positioned within a 1×1 mm area, appropriate spacing
for the rat M1 motor cortex. A fifth microwire (150 µmdiameter) aids in positioning the insertion shuttle for theproper insertion depth.

was sterilized in ethylene oxide gas for 24 hr at room
temperature. All procedures for the animal experiments werein accordance with the animal protocol approved by theHuntington Medical Research Institutes Institutional Animal
Care and Use Committee (HMRI IACUC) and incompliance with the Animal Welfare Act.

Figure 6. PSEA affixed to insertion shuttle with PEG. Scale bar = 6 mm.

III. RESULTS AND DISCUSSION
A. Electrochemical Testing
Following electrochemical cleaning with CV, EIS wasperformed on all electrodes in the array. Across theelectrodes, the EIS curves were very consistent, indicating avery reliable fabrication process (Fig. 7). At thephysiologically relevant frequency of 1 kHz, the impedance
magnitude was 148.6 ± 9.3 N for 32 electrodes in an array(mean ± SE).
B. Insertion Shuttle
For in vitro insertion tests, a 0.5% agarose gel brain
phantom was created to imitate the mechanical properties ofcortical tissue. The PSEA, affixed to the insertion shuttle
with PEG as described earlier, was implanted using amotorized inserter at 0.8 mm/s and the insertion site wasflushed with saline. After 5 min, the PEG was completely
dissolved and the insertion shuttle was retracted, leaving thePSEA in place (Fig. 8). Using the same protocol, the PSEA
was also successfully implanted into the rat M1 motor cortex
with the insertion shuttle and stereotactic mount (Fig. 9).
Prior to implantation, the PSEA-insertion shuttle assembly

Figure 7. Magnitude (a) and phase (b) of EIS measurements.
Mean ± SE, n = 32 electrodes.

IV. CONCLUSION
A 2×2 array configuration of the PSE was developed,
thereby successfully demonstrating the scalability of the PSE
technology and paving the way to electrode densities
comparable to those in the Utah Electrode Array and theMichigan Electrode Array. With this increase in electrodedensity and thus access to neuronal populations, we hope toestablish a more robust, reliable neural interface. Employing
data collected in a 28-day in vivo study, the sheath structuresof the PSEA were redesigned to minimize insertion trauma
and promote cell-cell signaling by introducing perforations
throughout the sheath structure. Along with the use of
bioactive coatings, it is expected that these design
FRQVLGHUDWLRQV ZLOO EHWWHU PLWLJDWH WKH EUDLQ¶V LPmune
response [10] and therefore improve long-term signal

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reliability. Benchtop electrochemical testing indicates thatthe electrode impedance values are suitable for neuralrecording. A customized insertion shuttle demonstrated
successful delivery of the flexible PSEA both in an agarose
gel brain phantom model as well as in the rat M1 motor
cortex. In vivo electrophysiological data is currently being
collected and the performance of the PSEA will be analyzed.
This work represents a vital step in the exploration of theimplementation and scalability of Parylene C technology tofabricate flexible neural probes for chronic recording.
Furthermore, it demonstrates the versatility of the PSE
technology to respond to developments in the neuralinterface field that call for novel probe shapes or surface
topologies.
ACKNOWLEDGMENT
The authors would like to thank Dr. Saiyun Hou at
Huntington Medical Research Institutes (HMRI, Pasadena,CA 91105) for performing the chronic animal implantations
and the members of the Biomedical Microsystems
Laboratory for their support.
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Figure 8. PSEA insertion (a) and shuttle retraction (b) in an agarose gel
brain phantom model. Scale bar = 3 mm.

Figure 9. PSEA insertion (a) and shuttle retraction (b) in the rat M1 motorcortex. Scale bars = 6 mm.

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