A PARYLENE CUFF ELECTRODE FOR PERIPHERAL NERVE RECORDING
AND DRUG DELIVERYAngelica M. Cobo1, Barbara Boyajian1, Christopher Larson1, Kee Scholten1, Victor Pikov2, andEllis Meng1*1
University of Southern California, Los Angeles, California, USA2
Galvani Bioelectronics, UK(geometric surface area of 0.45 mm2) embedded within fourParylene C microfluidic channels (Design 1, 250 µm W ×20 µm H). The cuff is designed to fit securely around a rat
sciatic nerve, and is held in position by etched serrations
which accommodate diameters between 1.1 to 1.5 mm in
0.1 mm increments (Figure 1).
Two separate fluidic channel designs were investigatedto improve mechanical robustness, particularly during
deformation, and allow uniform flow through all channels in
the curled orientation. Design 2 incorporates polymer
support walls along the horizontal channel as shown in
Figure 1b [11, 12]. Mid-channel support walls were
fabricated from Parylene along the horizontal feeder
channels at sites where channel collapse was previously
observed. Design 3 incorporates microfluidic channels withnarrower widths and lower aspect ratio (Figure 1c).

ABSTRACT
We present a novel polymer-based cuff electrodedesigned for peripheral nerve recording and drug delivery.
The micromachined cuff interface consists of platinum
electrodes embedded within Parylene microfluidics. An
adjustable locking mechanism ensures close-fitting of thecuff around the nerve for localized drug delivery to induce
axonal sprouting from the fascicles towards the embedded
electrodes. This Lyse-and-Attract Cuff Electrode (LACE)
specifically incorporates drug delivery to improvesensitivity, spatial resolution, fascicle selectivity, andchronic reliability over existing electrode-only interfaces.
We present the design, fabrication, and initial testing offully functional cuffs including evaluation of the locking
mechanism, localized drug delivery, and electrochemical
properties of recording electrodes.

INTRODUCTION
Prostheses for amputees based on implantable
peripheral nerve (PN) interfaces have the potential to restore
natural limb function and sensation [1-4]. Non-invasive PN
interfaces wrap around the circumference of nerves reducing
the risk of nerve damage and prolonging chronic
performance [1-3]. Given their exterior location relative tothe epineurium, these electrodes are largely insulated fromthe neural activity of individual axons, resulting in lower
signal-to-noise ratio (SNR) and selectivity. Better access tothe central axon population and improved targeting of
smaller axon groups has been achieved using penetratinginterfaces, but at the cost of greater invasiveness [5, 6].
LACE aims to achieve high fascicle selectivity while
maintaining a minimally invasive interface by inducing
collateral axonal sprouting from axons within the PN
fascicles towards the microfluidic channels by way oftargeted drug delivery. Lysing agents will be delivered to
the fascicles closest to the microfluidic outlet ports to
temporarily disrupt the epineurium, followed by delivery ofneurotrophic factors to promote axonal sprouting towards
electrodes embedded in the microfluidic channels [7-10].
The cuff incorporates an adjustable locking mechanism toensure close-fitting of the interface to nerves of varying
diameters and permit highly localized drug delivery. Thismethod will help realize a chronically stable PN interface
capable of high SNR recordings.

Figure 1: Schematic of LACE showing three different
microfluidic channel configurations that support channel
integrity when the cuff is curled: (a) Design 1: standardchannels (20 µm H x 250 µm W), (b) design 2:
incorporation of mid-channel supporting walls (20 µm H ×
20 µm W × 390 µm L), and (c) design 3: narrower channels(150 µm and 250 µm W sections).

FABRICATION
Devices were batch fabricated using standard Parylene
micromachining processes (Figure 2). Platinum was sputter
deposited (2000 Å thick) and patterned on a Parylene coated(10 µm thick) silicon wafer by a lift-off process. Following
deposition of a 10 µm Parylene insulation layer, sacrificial
photoresist (20 µm height) was patterned to establish themicrofluidic channel and the mid-channel support wallDESIGN
The polymer device supports pairs of Pt electrodes

978-1-5090-5078-9/17/$31.00 ©2017 IEEE506

MEMS 2017, Las Vegas, NV, USA, January 22-26, 2017

structures. A final 8 µm thick layer of Parylene was used toenclose the microfluidics, and access ports were patterned
and then opened with oxygen plasma.

Microfluidic Channel EvaluationMicrofluidic channels were evaluated in curled devices
by infusing colored dye at a 500 nL/min flow rate using an
external syringe pump (Harvard Apparatus Infuse/Withdraw
PHD 2000) and imaging the transverse progression of thedye with a microscope (Caltex Scientific HD60T). Flat
LACE devices were submerged in distilled water under the
microscope, and primed by flushing the channels withisopropyl alcohol and distilled water for 5 minutes each.
Devices were then curled, placed upright in an acrylic jig,
and submerged under distilled water while infusing the
microfluidic channels with a blue color dye.
Localization of fluid delivery was demonstrated bylocking prototype LACE devices around a simulated sciatic
nerve produced from a molded polydimethylsiloxane(PDMS) core covered with Kim-wipe, then driving blue
color dye through the microfluidic channels using a syringe
pump. The nerve phantom was selected to mimic the size ofa rat sciatic nerve for the purpose of facilitating
visualization during infusion studies. First, a PDMS core
was cut from a block using an 18G coring needle (0.97 mmID). This core was then circumferentially wrapped with twolayers of Kim-wipe, increasing the diameter of the nerve
phantom to approximately 1.3 mm, which falls in the sciatic
nerve diameter range of 1.2 – 1.4 mm reported for a 340 g
male rat. Devices were primed as previously described andthen curled around the nerve phantom. Color dye wasinfused at 100 nL/min until it reached the fluidic outlet
ports. The nerve phantom was imaged using an optical
microscope and digitally processed using ImageJ (NIH)software to correlate the color signal with localization. The
degree of localization of the infused fluid was quantified by
the location and dimensions of the dyed area.

Figure 2: LACE fabrication process which utilizes standard
surface micromachining techniques for Parylene.
Devices were released from the substrate and sacrificial
photoresist was removed with an acetone soak (Figure 3).
An electrical connection was established with a zero
insertion force (ZIF) connector, using previously reported
methods [13]. Device level fluidic packaging consisted of apolyether ether ketone (PEEK, part no. 1571, IDEX Health& Science) tubing secured in place with MED 4210 silicone
adhesive (Factor II Incorporated).

Figure 3: Photograph of fabricated LACE.

EXPERIMENTAL METHODSInterlocking Mechanism Evaluation
A LACE device was wrapped around the sciatic nerveof an anesthetized 260 g rat and its holding strength wasevaluated in vivo under handling conditions (Figure 4). The
sciatic nerve was then dissected with the LACE device
wrapped around it. All procedures for the animal
experiments were in accordance with the animal protocol
approved by the Animal Care and Use Review Office(ACURO).

Figure 4: Photographs of the LACE placement on thesciatic nerve. (a) Unlocked LACE on the sciatic nerve, (b)locked LACE on the sciatic nerve, and (c-d) locked LACE
on the dissected sciatic nerve.
Embedded Electrodes Evaluation
Electrochemical impedance spectroscopy (EIS) wasused to assess the recording capabilities of the electrodes.

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Electrochemical characterization of the electrodes wasperformed with a Gamry Reference 600 potentiostat (GamryInstruments, Warminster, PA). The electrode surface waselectrochemically cleaned with cyclic voltammetry (CV) in0.05 M H2SO4 prior to EIS measurement. LACE devices
were soaked in phosphate buffer saline (1× PBS) at room
temperature under vacuum for 1 hours to prime the fluidic
channels prior to EIS testing. EIS was performed with an
AC perturbation signal of 10 mV (rms) in the frequency
range of 1-105 Hz. An Ag/AgCl (3M NaCl) reference and 1
cm2 Pt plate counter were used.

Table 1: Average diameter of outlet port stain (n = 3).
Fluidic Port Diffusion Diameter(mean ± SE)
Device 1
0.209 ± 0.022 mm
Device 20.455 ± 0.058 mm
Device 30.310 ± 0.056 mmEmbedded Electrodes Evaluation
Electrochemical measurements on cuff electrodes
yielded acceptable electrical impedance for the referenceelectrode for PN recordings. As expected, electrodes thatwere embedded in the channels exhibited higher impedancevalues which is attributed to the limited ion diffusion
imposed by the surrounding fluidic channels (Table 2 andFigure 7). As these electrodes are intended to be used onaxons that have grown into the microchannels, the increased
impedance is not expected to adversely affect recordings.
Instead, the close proximity of a specific axon is expected toimprove nerve selectivity and signal fidelity.

RESULTS AND DISCUSSIONInterlocking Mechanism Evaluation
The locking mechanism was simple to implement androbust; no damage to the nerve or cuff was observed whenengaging and releasing the lock or after curling.
Microfluidic Channel Evaluation
Uniform flow through all fluidic channels and outlet
ports was achieved with design 2 (n = 3) (Figure 5b). Flowthrough some channels was blocked by pinching of thehorizontal feeder channel in designs 1 and 3 (Figure 5a &c). Design 2 will be selected for future animal testing.

Table 2: Electrochemical impedance spectroscopy in 1xPBS
at 1 kHz (mean ± SE). Partially embedded electrodes arelocated underneath the fluidic outlet port.
ElectrodenImpedancePhase(kΩ)(°)
No fluidics
22.94 ± 0.43
-59.76 ± 9.66
Partially embedded
8 14.27 ± 1.38 -35.16 ± 3.81
Fully embedded
8 44.94 ± 8.50 -18.10 ± 3.08

Figure 5: Representative photographs of the infusion
experiment in curled devices at 500 nL/min flow rate
(transverse view). The channels were primed with the dyeintroduced at the microfluidic inlet channel. (a) Design 1,(b) design 2, and (c) design 3. Scale bar is 1 mm.
Localized drug delivery on nerve phantoms wasconfirmed and is shown in Figure 6. Diffusion area wascharacterized by measuring the diameter of the outlet port
stain using ImageJ software (Table 1). Localized delivery
was achieved through at least three microfluidic channels
with differing flow rates among individual channels.
Consequently, the diffusion area for each channel is slightly
different even within the same device.

Figure 6: (a) Transverse view of LACE wrapped around anerve phantom. Insert shows side-view. (b) Representative
nerve phantom after localized dye delivery (n =3).

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Figure 7: Representative electrochemical impedance
spectroscopy plots of impedance magnitude and phase in
1xPBS for a (a) surface electrode with no fluidics, (b)partially embedded electrode (fluidic outlet port), and (c)fully embedded electrode.

CONCLUSION
We developed a novel Parylene-based PN interface
with the potential to achieve improved SNR, recording
selectivity, and prolong in vivo performance over existing
technologies. The adjustable locking mechanism proved tobe simple to implement and provided adequate holding
strength when wrapping or unwrapping around the rat
sciatic nerve. Redesigned microfluidic channels achieved
uniform flow through all channels, which is important fortargeting multiple fascicles within the nerve. Localized fluiddelivered was achieved at low flow rates. High EIS
impedance values obtained for the embedded electrodes are
attributed to the limited ion diffusion of the channels. The
close proximity of the axon to the electrode is expected toyield high quality neural recordings. Future work entails
long-term characterization of electrodes in simulated in vivo
conditions and in vivo animal testing.

ACKNOWLEDGEMENTS
This work was supported under DARPA cooperative
agreement HR0011-15-2-0006, Viterbi School ofEngineering Ph. D. Merit Fellowship (AC), and USC
Provost Fellowships (CL). The authors would like to thankDr. Donghai Zhu and the members of the USC BiomedicalMicrosystems Laboratory for their assistance with thisproject.

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CONTACT*E. Meng, tel: +1-213-8213949; ellis.meng@usc.edu509