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An Electrochemical Investigation of the Impact ofMicrofabrication Techniques on Polymer-Based
Microelectrode Neural Interfaces
Seth A. Hara, Student Member, IEEE, Brian J. Kim, Jonathan T. W. Kuo, and Ellis Meng, Senior Member, IEEE

Abstract— The electrochemical (EC) properties of microelectrodes on flexible polymer substrates can vary as a result of
microfabrication and postfabrication processes. These in turn
may impact the chronic recording performance of such electrodes. In this paper, electrochemical techniques were utilized forthe preparation and nonbiological evaluation of microfabricatedflexible neural probes consisting of platinum electrode recordingsites supported and insulated by Parylene C. The polymer
substrate mitigates the mechanical mismatch between neuraltissue and the probe. In addition, the thermoplastic nature of thepolymer enables the probe to be shaped postfabrication using
a thermoforming technique to impart a unique 3-D structurethat further promotes tissue integration and supports the use of
bioactive coatings. The EC techniques provided a simple means
to clean electrode surfaces (80.2% decrease in 1-kHz impedance),
identify functional devices, and evaluate their EC properties prior
to implant. Both electrochemical impedance spectroscopy andcyclic voltammetry measurements were performed on electrodesites following fabrication, cleaning, mechanical manipulation forassembly, thermoforming, and sterilization. The results reveal
in some cases changes in EC properties. Although changes
following thermoforming did not impact the ability to acquire
electrophysiological recordings, further investigation with additional tools is required to elucidate the exact nature of thestructural and EC changes resulting in the observed increasein impedance and reduction in electrode surface area following
thermoforming.
[2014-0378]
Index Terms— Brain-computer interface, cyclic voltammetry,electrochemical impedance spectroscopy, microelectrodes, neural
microtechnology, neural prosthesis.

I. I NTRODUCTIONCHRONIC intracortical recording reliability continues tobe a challenge in the design of neural prostheses.
In addition to nonbiological failure mechanisms such asdelamination of insulation, electrode breakage, or electrodecorrosion, current probe technology is susceptible to biological
failures which are believed to arise from immune responseto the presence of foreign material. Insertion trauma to theManuscript received December 12, 2014; revised March 16, 2015; accepted
May 7, 2015. Date of publication June 1, 2015; date of current version
July 29, 2015. This work was supported by the Defense Advanced
Research Projects Agency Microsystems Technology Office through theSpace and Naval Warfare Systems Center under Contract N66001-11-1-4207.
Subject Editor C. Ahn.
The authors are with the Department of Biomedical Engineering,
University of Southern California, Los Angeles, CA 90089 USA (e-mail:sethhara@usc.edu; brianjk@usc.edu; jonathtk@usc.edu; ellismen@usc.edu).
Color versions of one or more of the figures in this paper are available
online at http://ieeexplore.ieee.org.
Digital Object Identifier 10.1109/JMEMS.2015.2434827

Fig. 1.
Optical micrograph of the PSE, showing the placement offour electrodes inside of the sheath and four on the periphery.

neural tissue [1] and blood-brain barrier [2], chronic presenceof a foreign body in the tissue [1], [3]–[5], and the associatedchronic aggravation arising from the mechanical mismatch
between brain tissue and traditional rigid probes [6]–[8] haveall been linked to biological failures.
One tactic to mitigate biological failure is through the useof materials, such as polymers, with low Young’s moduli tobetter match the mechanical properties of brain tissue andalleviate the chronic irritation that mechanical mismatch cancause [6]–[8]. A different approach promotes dendritic growththrough the use of bioactive molecules to reduce the distance
between the signal source and recording sites [3], [9], [10].
Both of these strategies were implemented in the Parylene
Sheath Electrode (PSE; Fig. 1), an intracortical neural probefabricated on a Parylene C substrate. The PSE consists ofa three-dimensional (3D) open-lumen sheath structure withfour electrode sites situated on the interior surface of thesheath and four on the outer periphery, thereby leveraging the neurotrophic electrode (NE) approach invented by
Kennedy et al. [10], while also capitalizing on the benefitsof batch microfabrication using a thin-film polymer.
Microfabricated polymer probes may undergo uniqueprocessing compared to their silicon and ceramic counterparts.
This in turn may impact recording quality and should be
evaluated. Detailed characterization of electrodes is notoften reported, which restricts the long-term impact ofsuch technologies. Many groups have demonstrated the useof polyimide, an encapsulant commonly used in the
microelectronics industry, to create neural probes with multiple
metal layers and high electrode densities [11]–[14]. The probes
are formed by sandwiching thin-film metal between layersof polyimide and selectively exposing the electrode sites.
Another commonly used material, Parylene C (hereto referred

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See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.

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to as Parylene), is also compatible with standard
microfabrication techniques and is often used as both thesubstrate and insulation material for neural probes [15]–[18].
Parylene is especially of interest for application in neuralprobes due to its desirable barrier properties, ease of
deposition, thermoplastic nature, flexibility (Young’s modulusof 4 GPa [19]), mechanical strength, designation as a
USP Class VI material, and history of use in Food and Drug
Administration (FDA) approved implants [20]. To bring thesepolymer probe technologies to maturity, it is imperative tofully characterize their properties and understand how theirunique processing may affect their application in vivo.
Electrochemical (EC) techniques are commonly used tocharacterize electrode properties for neural probe applications. While EC methods may not be completely conclusive,
they are one of the few tools available for evaluation ofpolymer-based devices prior to implantation. Electrochemical
impedance spectroscopy (EIS) provides a measure of theelectrode impedance as a function of frequency, a parameter
often used to monitor the EC characteristics of the electrodeelectrolyte interface, and cyclic voltammetry (CV) is used
to electrochemically clean the electrode surface as well as
measure an electrode’s electroactive area. These tests are
typically conducted just prior to implantation to confirm
that the electrode properties are well-suited to their intended
application, whether that be recording or stimulation [21], but
are also powerful tools to investigate probe degradation [22].
The PSE utilizes novel fabrication techniques withpotential EC implications on electrode recording performance.
As polymer-based neural probes possess the potential tomitigate the chronic irritation to brain tissue [8], [23]–[25],it is necessary to evaluate the impact of fabrication techniques
on electrode recording performance and determine suitabilityof the fabrication techniques for adoption in chronic recording
probes. Preliminary characterization of the PSE was presented
in a prior study [26]. In this work, electrodes were evaluated by EIS following the complete fabrication of the probe
and at each step post-fabrication, including EC cleaning,thermoforming, and sterilization.
II. M ETHODS
A. Fabrication of the Parylene Sheath ElectrodeFor a complete description of the fabrication process, thereader is referred to our earlier work [27]. The process isbriefly summarized here.
The PSE was surface micromachined entirely from
Parylene and platinum. 5 µm of Parylene was deposited on asilicon carrier wafer with its native oxide layer intact using achemical vapor deposition (CVD) process (Fig. 2a). Circular
platinum (Pt) electrodes, traces, and contact pads were e-beamdeposited (200 nm thick) and patterned through a liftoff
process (Fig. 2b). Electrode sites were 45 µm in diameter, which is acceptable for single- and multi-unit recording
applications [21]. A 1 µm Parylene layer was deposited toinsulate the Pt traces and an O2 plasma etch exposed theelectrode sites and contact pads (Fig. 2c). A final 5 µm layerof Parylene was deposited over a photoresist sacrificial layer

Fig. 2. Cross-sectional illustration of the major fabrication steps for the
PSE with exterior electrodes located on the periphery of the sheath. (a)Silicon carrier wafer, (b) patterned platinum electrodes, (c) patterned Parylene
insulation, (d) Parylene deposition on photoresist sacrificial layer, and (e)dissolution of sacrificial layer to release microchannel.

Fig. 3. Illustration of the thermoforming process. A custom-tapered stainlesssteel microwire was inserted into the flat surface micromachined PSE (a) to
fully open the sheath structure (b). Following heat treatment, the microwire
was removed and the 3D sheath retained the desired shape (c).

to form the microchannel that becomes the sheath (Fig. 2d).
The electrode sites, contact pads, and both sides of the
Parylene microchannel were etched with O2 plasma. Finally,
the outline of the PSE was O2 plasma etched and the PSE
was released from the wafer; the presence of the native oxide
facilitates the release. The sacrificial layer was removed fromthe microchannel with an acetone soak (Fig. 2e). The final
outline etch was used to create different probe geometries,
one conical and the other cylindrical in shape, the purposeof which was to determine an optimal geometry to minimize
surgical trauma during implantation.
To create the 3D sheath, the flat microchannels weremolded by a thermoforming process (Fig. 3); the same process
also improves the adhesion between the multiple Parylene
layers [28], [29]. First, custom-tapered stainless steel
microwires were inserted into the microchannel. With themicrowires in place, the wire-channel assemblies wereannealed at 200 °C for 48 hours under vacuum. The
temperature was then slowly ramped down to room temperature and the microwires were removed, leaving the 3D sheathsin the desired shape. This heat treatment process alters the
crystallinity of the Parylene, allowing it to permanently adopt
the shape of its mold [30].
B. Ethylene Oxide Sterilization
In a concurrent in vivo study, the PSE was sterilized with
ethylene oxide (EtO) prior to implantation. To determine theEC effects of this process, the PSE was EC tested before andafter sterilization. Sterilization was performed at room temper-

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ature with the Anprolene AN74i sterilizer system (Andersen
Products, Inc., Haw River, NC) using a 24 hour cycle.
C. Electrochemical Techniques
CV was used to both provide a measure of the electroactive surface area and to produce a clean electrode surface
prior to further testing. EIS was then used to measure theelectrode impedances at various points of the fabrication
process. To conduct the EC measurements, a Gamry Reference
600 potentiostat (Gamry Instruments, Warminster, PA) wasused with a Faraday cage to minimize noise. To overcome
the hydrophobicity of Parylene that prevents the filling of
the probe’s conical sheath structure, the Parylene surface was
first wetted with isopropyl alcohol prior to immersion in
the measurement solution. Each electrode was subjected toa single experimental trial in each sample set.
In addition to standard microfabrication cleaning techniques(repeated rinses with acetone, isopropyl alcohol, and deionizedwater), CV was used to electrochemically clean the electrodesurface, as described by Petrossians et al. [31]. This provides
the same oxidation/reduction process as voltage pulsing usedin other EC disciplines [32]–[37], but in a less aggressive
manner. Using a three-electrode cell, electrodes were
immersed in 0.05 M H2 SO4 with constant N2 purging. The
working electrode was cycled between −0.2 to 1.2 V withrespect to an Ag/AgCl (3M NaCl) reference, a potential rangethat is within the water window [38]. A 1 cm2 Pt plate served
as the counter electrode. Using a scan rate of 250 mV/s, eachelectrode was cycled for 30 cycles at which point the curves
reached a steady-state, indicating that no further cleaning was
occurring.
EIS was performed in phosphate buffer saline (1× PBS)
at 37 °C with an AC perturbation signal of 10 mVrms in
the frequency range of 1-105 Hz. As with CV, an Ag/AgCl(3M NaCl) reference and 1 cm2 Pt plate counter were used.
Thewell-understoodredox
behavioroftheferricyanide/ferrocyanide couple was utilized to investigate thepossibility that thermoforming obscures the electrode surface,which may account for the observed electrochemical changes
in the EIS and CV results. This redox couple is often usedwith CV as it is a relatively uncomplicated model of a highly
reversible reaction [39]. To this end, a CV in freshly-prepared
6 mM potassium ferrocyanide (K4 [Fe(CN)6 ]) was conductedwith a scan rate of 50 mV/s from −0.1 to 0.5 V vs. Ag/AgClwith a 1 cm2 Pt plate counter electrode.

Fig. 4. Representative CV of probe following microfabrication. Mean ± SE,
n = 8 electrodes on a single cylindrical sheath geometry probe. Inset: SEM
of electrode surface, showing native roughness.

Fig. 5. EIS magnitude plot both prior to (black) and after white) electrochemical cleaning. Data was taken before thermoforming. Cylindrical sheath
geometry. Mean ± SE, n = 40 electrodes on 5 probes.

III. R ESULTS
A. Electrochemical Cleaning
EC cleaning of the electrodes produced CV curves such as
the one seen in Fig. 4. By integrating the hydrogen desorption
portion of the curve and utilizing the commonly accepted
conversion factor of 210 µC/cm2 [40], the electroactive surface
area of the curve was calculated to be 19,567 µm2 . The
geometric surface area of the electrodes was 1590 µm2 ,suggesting a roughness factor of 12.
EIS measurements were taken on pre-thermoformed probes
both prior to and after being EC cleaned. As was observed

Fig. 6. EIS phase plot both prior to (black) and after (white) electrochemicalcleaning. Data was taken before thermoforming. Cylindrical sheath geometry.
Mean ± SE, n = 40 electrodes on 5 probes.

by Grand et al. [37], electrode impedance decreased(Fig. 5 and Fig .6). The initial cleaning procedure resulted
in a 1 kHz impedance magnitude drop of 80.2% (Table 1),

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TABLE IC OMPARISON OF 1 kHz I MPEDANCE M AGNITUDE VALUES B EFORE
AND A FTER E LECTROCHEMICAL C LEANING . C YLINDRICALS HEATH G EOMETRY, P RE -T HERMOFORM :N = 40 E LECTRODES ON 5 P ROBES

variation between electrodes was reduced, discontinuities
observed in the phase curve were removed, and the expected
impedance response was obtained.
B. Mechanical Opening of Sheath
The formation of the 3D sheath structure required
mechanical opening of the initially flat microchannel with acustom-tapered microwire followed by an annealing process.
Mechanically opening the microchannel temporarily formed
the sheath, but deformation returned the sheath to its initial flat
shape. The mechanical opening step was studied with EIS oncethe microwire was removed, but prior to any deformation,
to confirm that the expansion of the microchannel did notadversely impact EC performance of the electrodes. As theplacement of the electrodes either inside of the sheath or on the
periphery can also alter their EC performance, the effects ofmechanically opening the sheath were studied on each groupseparately. As can be seen in Fig. 7, the outer electrodes
were unaffected by opening of the sheath. The inner electrodes(Fig. 8) exhibit a slight decrease in impedance, likely due tothe widening of the conductive path to the counter electrodefollowing expansion of the sheath structure. Similar results
are expected in different geometries. The cylindrical sheath
geometry has an internal sheath volume that is 122% larger
than the conical sheath geometry and the impedance change
due to mechanical opening of the sheath is expected to scaleaccordingly, that is, a larger internal sheath volume correlates
to a larger conductive path and thus lower solution resistance.
C. Heat Treatment
Upon EC testing of the PSE following thermoforming, it
was discovered that the process significantly changed the EC
properties of the electrodes (no significant difference under
optical or electron microscopy observation). As seen in Fig. 9,
the impedance magnitude of the electrodes after the heat
treatment process is greater at lower frequencies and changes
slightly in slope. The impedance phase (Fig. 10) shifted
towards lower frequencies and became slightly more negative.
CVs conducted in ferrocyanide revealed a distinct differencein electrode performance between electrodes tested prior toand those tested after undergoing the heat treatment process.
As observed in Fig. 11, there was a dramatic drop in current
following heat treatment.
D. Effects of Ethylene Oxide Sterilization
Testing before and after the EtO sterilization process
showed no impact on the performance of the elec-

Fig. 7.
EIS comparison of outer electrodes before (black) and after(white) mechanically opening the sheath. Magnitude curve is represented bysquare markers, phase by circles. Cylindrical sheath geometry. Mean ± SE,
n = 8 electrodes on 2 probes.

Fig. 8.
EIS comparison of inner electrodes before (black) and after(white) mechanically opening the sheath. Magnitude curve is represented bysquare markers, phase by circles. Cylindrical sheath geometry. Mean ± SE,
n = 8 electrodes on 2 probes.

trodes (Figs. 12 and 13). The minor differences seen in the EIS
curves manifest themselves only at high frequencies, where thesolution impedance dominates the system response.
IV. D ISCUSSION
In this study, we demonstrated the importance of
EC cleaning to produce pristine electrode surfaces forrecording. Although microfabricated neural probes have been
implanted since 1970 [41], based on research literature, they
are not systematically cleaned by electrochemical methods
prior to implant. In various other subgenres of electrochemistry, electrochemical cleaning techniques are used to produce
clean electrode surfaces. By anodizing the electrodesurface and forming an oxide layer, any contaminants
that are adsorbed to the electrode surface are removed.
Subsequently reducing that oxide layer produces a clean
electrode surface [32]. This technique has previously been
demonstrated for the in situ reduction of bacterial biofoulingHARA et al.: EC INVESTIGATION OF THE IMPACT OF MICROFABRICATION TECHNIQUES

Fig. 9. Impedance magnitude of a PSE before (black) and after (white)heat treatment. Conical sheath geometry. Mean ± SE, n = 15 electrodes on
2 probes.

Fig. 10.
Impedance phase of the PSE before (black) and after (white)heat treatment. Conical sheath geometry. Mean ± SE, n = 15 electrodes on
2 probes.

of surfaces in the food and marine industries [33], [34].
For neural probe applications, Otto et al. made a case forrejuvenation of a neural electrode in vivo [35] through voltage
pulsing, but this technique is designed to mitigate biofoulingof the electrode surface and not removal of contaminants prior
to implantation. As seen in Fig. 5 and Fig. 6, EC cleaning
prior to testing eliminates abnormalities, leading to improved
repeatability between devices.
Ulbert et al. mention the use of voltage pulsing to “remove
debris from electrode sites possibly built up during storage
and sterilization,” [36] and this same group later showed a
50% decrease in 1 kHz impedance as a result of this voltage
pulsing on a silicon-based neural probe [37]. It was observedthat this style of voltage pulsing is potentially destructive
for thin-film electrodes on a Parylene substrate, leading todetachment of the electrodes from the Parylene (data notshown). For this reason, CV was used to EC clean the electrodesurfaces without damaging them.
Despite the fact that the PSE probes were cleaned withstandard microfabrication techniques (and appeared clean

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Fig. 11. CVs taken before (black solid line) and after (red dashed line)
heat treatment. Conical sheath geometry. Mean ± SE, n=16 electrodes on
2 probes.

Fig. 12. Impedance magnitude of the PSE before (black) and after (white)sterilization. Conical sheath geometry. Mean ± SE, n = 36 electrodes on
5 probes.

by visual inspection under an optical microscope), it wasevident that debris, possibly in the form of photoresist scum,remained on electrode surfaces after fabrication, highlighting
the importance of this additional EC cleaning step prior
to probe implantation. Removal of this debris is critical as
the debris obstructs the electrode surface and impedes ion
exchange at the electrode-electrolyte interface, thereby attenuating recorded neural signals. These data indicate the importance of additional cleaning of microfabricated electrodes toremove residual contaminants that may obstruct the electrodesurface.
In the first generation PSE, the outer electrodes werepositioned on top and in the midline of the sheath. The
mechanical process used to form the three dimensional sheathexerted a tensile stress on these electrodes in addition to theexisting tensile stress imposed on the electrodes as a result of
the deposition process [42], [43] and therefore occasionallyresulted in electrode cracking. This cracking manifested asincreased impedance magnitude of the outer electrodes compared to inner electrodes and shifted phase or multiple time

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Fig. 13.
Impedance phase of the PSE before (black) and after (white)sterilization. Conical sheath geometry. Mean ± SE, n = 36 electrodes on
5 probes.

constants in the EIS characterization. Optical microscopy andSEM confirmed the presence of cracks across these electrodes,
leading to redesign of the PSE (2nd generation), placing theouter electrodes on the periphery as opposed to the top of
the sheath (Fig. 1). This placement could result in improved
recordings as the electrodes could benefit from reduced encapsulation and increased proximal neuronal density compared toother locations on the PSE [44].
Although EIS alone is not sufficient to identify electrodecracking on its own, it is a useful tool that may be used inconjunction with microscopy to diagnose this issue unique to
3D polymer-based electrodes. Also, EIS is more amenable tohigh throughput evaluation of electrode quality and may prove
useful as a screening technique for selecting devices suitablefor implantation.
The current (2nd generation) PSE design, with theouter electrodes located at the periphery, did not exhibit
EC performance differences between inner and outer electrodes following mechanical opening of the sheath. The slightdecrease of impedance seen with the inner electrodes wasobserved at higher frequencies, where the solution impedanceis the dominant parameter. This suggests that the impedance
decrease may be explained by the widening of the conductive
path between the electrode sites and the external Pt counterelectrode. The radius of curvature for the conical sheath
geometry ranged from 20 µm to 100 µm and was 250 µm
for the cylindrical sheath geometry. The placement of theelectrodes was such that they only experienced this curvature while under compressive strain. The data indicated thatthin-film Pt electrodes in this configuration retain desirable
EC characteristics.
The second part of the 3D sheath formation process usedin this work, the heat treatment process, has previously
been shown to promote adhesion of Parylene layers andimprove insulating performance [28], [29]. While the effectof the heat treatment process on exposed electrode sites was
not investigated in their work, Rodger et al. demonstrated
successful usage of their heat-treated devices in vivo to

Fig. 14.

Equivalent electrical circuit used to model the PSE.

stimulate neurons. In this study, it was found that the process
alters the EC properties of the PSE. Although the exact
causes of these changes cannot be deduced from these results,
a few possibilities are suggested. The increase in impedance
observed at low frequencies could indicate a decrease inelectrode area, which correlates well with what is observed in
the ferrocyanide CV. This could be caused by the depositionor formation of an occluding substance onto the electrodesurface during the heat treatment process that is not visible
with standard SEM imaging.
Another possible explanation that could contribute to theobserved increase in impedance could be the sealing ofParylene layers at exposed interfaces. Prior to heat treatment,
it is possible that gaps exist between the Parylene layers due
to inadequate adhesion between the layers. As a result, oncethe devices are immersed, the solution would be in contact
with more of the metal surface than intended, producing alower measured impedance. As the annealing improves theadhesion between the two Parylene layers, these gaps would
lessen or disappear, resulting in less metal surface exposed tothe solution, and thus, a higher measured impedance. In an
attempt to identify the changes occurring at the electrodesurface, energy-dispersive X-ray spectroscopy (EDX) and
X-ray photoelectron spectroscopy (XPS) measurements wereconducted, but proved inconclusive; the penetration depth of
the EDX was too great and the spot size of the XPS was
too wide to produce a reliable signal just from the electrodesurface.
Modeling of the EIS data may help interpret the observedchanges. The data sets exhibited two time constants, prompting the use of an equivalent electrical circuit model that
includes a coating capacitance in parallel with a simplified
Randles circuit (Fig. 14) [45], [46]. This capacitance models
the effects of a non-conductive film on the electrode, suchas the insulating Parylene layer along the traces of theprobe, which may introduce a second time constant tothe system. Constant phase elements were used in themodel in place of capacitors to better represent the surface
inhomogeneities [47]. Modeling software (Echem Analyst,

HARA et al.: EC INVESTIGATION OF THE IMPACT OF MICROFABRICATION TECHNIQUESTABLE IIC ALCULATED C OMPONENT VALUES F ROM M ODELED EIS D ATA

Fig. 15. Pre-heat treatment measured impedance data (magnitude, square
markers; phase, circle markers) and model fit (dashed red line).

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resistance components. The increase in Faradaic resistanceand decrease in Faradaic capacitance are consistent with adecrease in exposed electrode surface area, as indicated byprevious observations, but the value of the Faradaic capacitance may yield an explanation as to what caused the decreasein electrode area. The theoretical capacitance of thin film
platinum microelectrodes in physiological saline has been
calculated to be 0.545 pF/µm2 [48]. For our designed electrodearea of 1590 µm2 , this equates to a capacitance of 0.9 nF.
Although the theoretical calculation does not account forsurface roughness, it is expected that the observed electroderoughness would result in a larger capacitance. The Faradaic
capacitance modeled from the data approaches the designed
theoretical value following heat treatment, suggesting that the
exposed electrode surface approaches the desired electrodearea. The reduction of Rpore further supports this conclusion.
Complete removal of this parameter from the model would
result in a modified Randles model, a commonly acceptedmodel for a metal electrode in solution, indicating that thesealing of the Parylene layers effectively removes the “pores”
that are responsible for the pore resistance element. As thisphenomenon is of interest for all Parylene-metal-Parylene
devices, new studies are being designed that will further
test this hypothesis in test structures. Nonetheless, despite
these EC changes, the electrodes successfully obtained neuralrecordings over the course of a month-long implantation in the
rat motor cortex [49]. Longer studies have been completed andthe data is under analysis.
Lastly, it was demonstrated that the EtO sterilization processthat was used for in vivo studies prior to implantation had noeffect on the EC performance of the PSE. Minor changes wereobserved in the EIS curve taken after sterilization, but thesechanges were isolated to high frequencies where the solution resistance dominates the system response. This change
is clearly the result of differences in solution conductivity,
due to slight variation in the measurement solution ionicconcentration.
V. C ONCLUSION

Fig. 16. Post-heat treatment measured impedance data (magnitude, square
markers; phase, circle markers) and model fit (dashed red line).

Gamry Instruments, Warminster, PA) was used to calculate
the values of the model components, which are detailedin Table 2, and the resulting fits are compared to the data setsin Fig. 15 and Fig. 16.
Based on the model, the changes observed after the heat
treatment process are consistent with a sealing of the Parylene
layers at the exposed interfaces. The dominant changes occur
in the Faradaic resistance, Faradaic capacitance, and the poreIn this work, microfabrication techniques of flexible neuralprobes were studied through the use of electrochemical
methods. An EC cleaning procedure conducted following
standard cleanroom cleaning procedures was shown to
reduce electrode impedance and correct abnormal impedance
performance without causing damage to the electrodes. These
results suggest that residue may remain on neural probes
from the microfabrication process and that an EC cleaning
procedure may be useful in removing such residues prior
to implant. EC testing of the PSE indicated that neither
the sterilization process nor the mechanical opening of the
Parylene microchannel to form the sheath structure had any
detrimental effect on the EC performance of the electrodes,
provided that the electrodes were not subjected to tensile
strain. The heat treatment portion of the thermoforming
process, however, resulted in performance variation as the
impedance spectra shifted and the current was attenuated in the
ferrocyanide CV. It is suspected that the observed EC changes

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are due to the sealing of the Parylene layers at the exposedinterfaces caused by the heat treatment process, but further
work must be conducted to elucidate the mechanisms atplay. In spite of these EC variations, as was shown by othergroups, the functionality of the electrodes remained intact. The
PSE successfully recorded neural signals in vivo over thecourse of a month-long implantation, indicating that the techniques utilized in the production of the PSE can be used for the
fabrication of future generations of 3D polymer neural probes.
ACKNOWLEDGMENT
The
authorsthank
Drs.
CurtisD.
Lee,
Christian A. Gutierrez, and Tuan Q. Hoang for theirassistance on the project, Dr. Victor Pikov at the Huntington
Medical Research Institutes (HMRI, Pasadena, CA 91105)
for his insight and advice, as well as Dr. Donghai Zhu (USC)
and the members of the Biomedical Microsystems Laboratory
for their support.
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Seth A. Hara received the B.S. degree in engineering from Swarthmore College, Swarthmore,in 2008, and the M.S. degree in biomedical
engineering from the University of Southern
California, Los Angeles, in 2013, where he iscurrently pursuing the Ph.D. degree in biomedical engineering with the Biomedical Microsystems
Laboratory. His research interests are in the development of implantable Parylene-based microelectromechanical systems devices, in particular, on theelectrochemical characterization and reliability of
Parylene-based electrodes. He was a recipient of the NSF Graduate
STEM Fellowship in K-12 Education in 2013.

809

Brian J. Kim received the B.S. degree
double majoring in biomedical engineering andmathematics from Duke University, Durham, andthe M.S. degree in biomedical engineering from the
University of Southern California (USC),
Los Angeles, in 2010 and 2013, respectively,
where he is currently pursuing the Ph.D. degree inbiomedical engineering (Provost’s Ph.D. Fellow)
with the Biomedical Microsystems Laboratory.
His research interests are in the development ofParylene-based microelectromechanical systems
devices for intracortical applications, in particular, on implantable Parylenebased sensor systems. He was a recipient of the Howard G. Clark
Award for Independent Research from Duke University, the Viterbi
School of Engineering Early Ph.D. Fellowship, and the USC Provost’s
Ph.D. Fellowship.

Jonathan T. W. Kuo received the B.S. degree inbioengineering from the University of California at
San Diego, in 2007, and the Ph.D. degree in biomedical engineering from the University of Southern
California, Los Angeles, in 2013. He was a recipientof the Viterbi Dean’s Doctoral Fellowship during his
graduate studies.

Ellis Meng (M’02–SM’09) received the B.S. degree
in engineering and applied science, and the
M.S. and Ph.D. degrees in electrical engineering from the California Institute of Technology(Caltech), Pasadena, in 1997, 1998, and 2003,
respectively. She has been a Professor with the
Department of Biomedical Engineering, Universityof Southern California, Los Angeles, since 2004. She
currently holds a joint appointment with the Ming
Hsieh Department of Electrical Engineering. Her
research interests include bioMEMS, implantablebiomedical microdevices, microfluidics, multimodality integrated microsystems, and packaging. She held the Viterbi Early Career Chair in the Viterbi
School of Engineering. She is a Member of Tau Beta Pi, the Biomedical
Engineering Society, the Society of Women Engineers, and the American
Society for Engineering Education. She was a recipient of the Intel Women in
Science and Engineering Scholarship, the Caltech Alumni Association Donald
S. Clark Award, and the Caltech Special Institute Fellowship. She has also
received the NSF CAREER and Wallace H. Coulter Foundation Early Career
Translational Research Awards. In 2009, she was recognized as one of theTR35 Technology Review Young Innovators under 35.