FABRICATION OF 3D PARYLENE SHEATH PROBES FOR RELIABLE
NEUROPROSTHETIC RECORDINGS
J.T.W. Kuo1, B.J. Kim1, S.A. Hara1, C. Lee1, C.A. Gutierrez2, T. Hoang1, and E. Meng1*
1
University of Southern California, Los Angeles, California, USA
2
Los Angeles, California, USAapproaches. Finally, the use of appropriate bioactive coatings canreduce inflammatory response and promote integration into tissue.
To achieve a stable long-term intracortical interface, weintroduce a novel microfabricated structure consisting of a hollow
sheath in the form of a cone or cylinder that can be decorated withmultiple biologically functional coatings (NGF, collagen, Matrigel,etc.) to mitigate the inflammatory response and attract andmaintain growth of neural processes toward recording sites (Figure1). Openings at the ends of the sheath further facilitate ingrowth ofneural processes after recovery from implantation toward
recording sites and tissue integration.

ABSTRACT3D Parylene sheath probes having Pt electrodes on the outerand inner surfaces of the sheath are introduced as a novel interface
for long term intracortical neural recording.
Surfacemicromachined Parylene channels with Pt electrodes are expanded
into a 3D sheath structure by thermoforming in the presence of acustom tapered microwire that shapes the sheath. Electrochemical
characterization,
includingelectrochemical
impedance
spectroscopy (EIS) and cyclic voltammetry (CV), of the Pt
electrodes sites was performed. EIS yielded electrode impedances
ranging from 20-60 kΩ at 1 kHz. Electrode characterization results
suggest the thermoforming process does not impact electrode
performance and were in agreement with characteristics of typicalneural recording electrodes. These sheath probes with their 3D
structural design, soft biocompatible materials, and bioactive
coatings promote integration with neural tissue enabling reliable,long term cortical recordings.

INTRODUCTION

Figure 1: Conceptual drawing of Parylene sheath probe for longterm intracortical recordings. A wire is inserted into the sheathand used as a surgical introducer to implant the device into thecortex (left). The wire is then removed and ingrowth of neuralprocesses following release of bioactive coatings facilitates longterm stable recordings (right).

Brain-machine interfaces for controlling motor prostheses
require reliable chronic recordings from intracortical
microelectrodes. Current microelectrode technologies arehampered by signal degradation over time that are attributed in partto neurotoxic factors released by microglia due to inflammatory
response arising from the mechanical mismatch between theimplanted rigid probe and cortical tissue; this leads to gradualretraction of neural processes from recording sites [1].
Intracortical microelectrode technologies possess short
lifetime in terms of acceptable recording quality (<5 years). There
are two such microelectrode formats that have been used in clinicalstudies. The first was constructed of tapered-tip silicon pins with asingle electrode at the tip [2-5]. Thermomigration was used tocreate trails of p+ type silicon through a wafer which were exposedby removal of n-type silicon to create arrays of needles that aresubsequently coated with platinum. Glass cone electrodes inwhich the cones are manually fabricated from pulled pipettes haveachieved the most reliable long term recordings in human to date
[6-12]. Microwires with de-insulated tips placed into the coneinterior at different depths serve as the recording sites, with 2-4wires per cone. Living sciatic nerve tissue or neurotrophic factors
were placed within the cones prior to implantation. The ingrowthof dendritic processes into the cone toward cortical recording sites(~3 months) were attributed to the release of neurotrophic factors.
Although, long-term recording reliability was achieved, manual
fabrication of the device is labor intensive and not amenable tomanufacturability nor increase in the number of recording sites.
Improvement in long term intracortical recordings isnecessary to realize practical neural prostheses. Criticalconsiderations in neural interface design include selection of
appropriate biocompatible structural materials to alleviate themechanical mismatch with tissue. Repeatability across devices andbatch fabrication can be achieved by using microfabrication
technologies. The used of thin film microfabricated electrodes also
increases the number and density of recording sites per probe,
while minimizing footprint, in order to acquire greater
spatiotemporal signal information compared to microwire

9780964002494/HH2012/$25©2012TRF

METHODS
Material Selection
Parylene C, a Class VI biocompatible polymer that can beprocessed with standard micromachining technologies [13], wasselected as the sheath probe structural material. The use ofParylene C mitigates mechanical mismatch issues between rigid
probe and soft tissue present in previous technologies. Parylene C
is flexible and much more pliable than stiff materials such as Si
and glass possessing a low Young's modulus [14].
Only Pt was used for electrodes since no adhesion layer isneeded with a Parylene substrate [15]. Pt is also highlybiocompatible and widely used in bioMEMS neural interface
applications [16-17].
Device Design
Sheath probes are cone or cylinder shaped with 4 Pt
electrodes (45 µm diameter) on each of the inner and outersurfaces. An integrated flexible Parylene cable (~2 cm long) isincluded. Sheath dimensions and electrode placement wereselected to match the neural anatomy of the barrel cortex in rat foreventual neural recordings to capture vibrissal (whisker)
movements.
The barrel cortex is organized into distinct regions that map toindividual vibrissae. Individual vibrissae movements are mediatedby neurons in layers V and VI of the barrel cortex throughgeneration of action potentials. These layers are located at a depthof ~1.5-2.0 mm in the rat brain and span ~800 µm in height [18].
Thus, the sheath structure was designed to be 800 µm in length tospan the targeted pyramidal layers. Electrodes were spaced
equidistant from each other within the sheath length in order toeffectively capture neural signals spanning the two layers.

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Solid-State Sensors, Actuators, and Microsystems Workshop
Hilton Head Island, South Carolina, June 3-7, 2012

controlled temperature ramp up to 200 °C for 48 hours withnitrogen purging. After thermoforming, the wire was removed andthe sheath retained its 3D shape (Figure 4).
Thermoforming not only provided the desired 3D shape but
also annealed the Parylene layers [20]. This improves the adhesion
between Parylene layers. Just prior to implantation, the sheaths arecoated with neurotrophic factors. A zero insertion force (ZIF)
connector was used to establish reversible electrical connections to
the microelectrodes of the sheath through the contact pads at theend of the integrated Parylene ribbon cable (Figure 5) [21].

Fabrication
A silicon substrate was used for mechanical support during
the fabrication process (Figure 2). A 5 µm Parylene layer was first
deposited onto the substrate to serve as the base layer of thedevice. Inner sheath e-beam deposited Pt electrodes (2000 Å) werethen patterned by a liftoff process with negative photoresist AZ
5214 E-IR. These electrodes will record from dendritic processes
extending into the sheath. A 1 µm Parylene insulation layer wasthen deposited and selectively plasma etched to expose electrodes
and contact pads. Sacrificial photoresist AZ 4620 was spun to aheight of 8 µm and patterned to form the sheath structures. A 5 µm
Parylene layer was then deposited over the photoresist.
Outer electrodes were patterned on top of the sheath structureusing a dual layer liftoff scheme. AZ 1518 was first spun on andglobally exposed. AZ 4620 was then spun on and patterned withthe top electrodes. This dual photoresist AZ 1518/AZ 4620 layer
scheme produced a negative sidewall profile that enhances theliftoff process for thicker photoresists and was necessary to ensure
a continuous pattern from the top of the structure to the base [19].
As with inner electrodes, Pt was e-beam deposited (2000 Å) for
outer electrodes. A final 1 µm Parylene insulation layer was
deposited and plasma etched to create openings for outerelectrodes and contact pads. Plasma etching then created sheath
openings and the device cutout. Sacrificial photoresist wasremoved with an acetone soak and the device was released fromthe substrate.

Figure 3: Custom tapered stainless steel wire for insertion into
sheath for thermoforming.

Figure 4: The sacrificial layer was first released (left).The tapered
wire was inserted into the sheath (middle) and the structure wasthermoformed. After thermoforming and removal of the wire, thesheath held its 3D shape (right).

Figure 5: Sheath probe with integrated Parylene cable is attached
to a ZIF connector for external electrical connection.

RESULTS
3D Sheath Probe Fabrication
Sheath probes were successfully fabricated with integrated
Parylene ribbon cables (Figure 6). In total, five different design
variants were fabricated for eventual use in rat whisker
intracortical recordings through the barrel cortex (Table 1).
Figure 2: Abbreviated fabrication process which utilizes standard
surface micromachining techniques followed by thermoforming.
Final outline of device is shown throughout process for clarity.
Parylene Thermoforming
A custom tapered stainless steel or tungsten microwire wasused as a mold for thermoforming of the conical or cylindricalstructure (Figure 3). Microwires were etched to match the desiredprobe shape and supplied by MicroProbes for Life Science. The
shaped microwire tip was carefully inserted into the sheathunderneath a microscope. The wire and device were placed in avacuum oven and the Parylene sheath was thermoformed by

Figure 6: Photograph showing layout of unreleased probe withintegrated cable still covered with photoresist. The verticalartifacts appearing along the length of the ribbon cable are due tostitching of images to obtain a view of the full length of the probe.

31

microelectrodes supported on thin Parylene films, could be directly
implanted into agarose (0.5%) models of neural tissue without
additional mechanical support.

Electrodes were placed to match the targeted cortical layers. 4
different cone shapes with different tapers ending at a 50 µm
opening were fabricated in order to test the effect of different
geometries on dendritic ingrowth, if any (Figure 7). A cylinder
structure was also fabricated.

Outer Sheath Surface Electrodes
In all designs, fabrication of the outer surface electrodes wasachieved successfully with the dual photoresist layer liftoff method
despite the nonplanar nature of the structure. Visual inspection
through microscopy showed no discontinuity between the lead
traces from the top of the structure to the bottom. Thermoformed
devices exhibited no discontinuities in leads to the outer surface
electrodes despite the increased strain.
A microprobe attached to a micromanipulator was carefully
positioned over an electrode on the outer cone surface while
another was positioned over the corresponding contact pad on theParylene cable. A Keithley 2700 MultiMeter was used to measure
the lead resistance which was observed to range from 325-389 Ωacross all leads. Conductivity between the electrode and contact
pad confirmed electrical continuity as leads transition from thebottom to the top of the sheath.

Table 1: Dimensions of the different fabricated sheath structures.
Electrode placement and dimensions remained constant for all
device variants.
DeviceNomenclature
AB
C
A-T
B-T

Base Opening
Diameter
300 µm450 µm300 µm500 µm
650 µm

Tip Opening
Diameter
50 µm
50 µm
300 µm
50 µm
50 µmSheath
Length800 µm800 µm800 µm800 µm800 µmCyclic Voltammetry
Cyclic voltammetry (CV) of Pt electrodes was conducted on aGamry Reference 600 potentiostat (Figure 8). The sheath probe
was placed in a 0.05 M solution of sulfuric acid (H2SO4) with oneof the Pt electrodes used as the working electrode. An Ag Ag/Clelectrode in a 3 M NaCl solution was used as a reference electrode.
An adjacent Pt electrode was used as the counter electrode. A scanrate of 250 mV/sec was used and cycled from -0.2 to 1.2 V until
stable voltammograms were achieved. The resulting stable
voltammogram was recorded and the procedure was repeated forthe remaining Pt electrodes.
The standard voltammogram for Pt immersed in sulfuric acidwas achieved for all electrodes. Oxide reduction and oxidation
peaks were clearly observed as well as the hydrogen peaks
indicating desorption and adsorption from the Pt surface. Thus,
electrical connections from the ZIF connector to the contact pad
through the Parylene cables to the recording site was verified to beelectrically conductive. Micromachined thin film Pt was validated
to possess the same properties as a bulk Pt microwire and so can beexpected to yield similar neural recordings.

Figure 7: Photographs of the different sheath designs. Each device
has been thermoformed. Electrode placement matches rat barrel
cortex anatomy.

Figure 8: CV in H2SO4 of single recording site yielded standard Pt
electrode characteristics.

Thermoformed sheaths were mechanically robust and unlike

Electrochemical

32

impedance

spectroscopy

(EIS)

was

performed on the electrodes with the sheath probe immersed in 1X
phosphate buffer solution (PBS). A representative measurement fora single electrode site is shown in Figure 9.

Judy through the Space and Naval Warfare Systems Center, Pacific
Grant/Contract No. N66001-11-1-4207.

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Figure 9: EIS of a single Pt recording electrode immersed in 1X
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CONCLUSION
We introduced a novel 3D Parylene sheath probe that wasmicromachined and then thermoformed for intracortical neuralrecordings. Compared to earlier glass cone electrodes, this process
was able to produce devices having repeatable dimensions in abatch process. Microfabrication also enabled greater yieldcompared to manually made cone electrodes. Parylene C wasselected as the structural material for its biocompatibility andimproved mechanical matching to tissue compared to rigid Si andglass.
Sheath structures were fabricated with electrodes at the outerand inner surfaces. Sheath dimensions and electrode placement
were designed to match rat barrel cortex neuroanatomy. Prior toimplantation in the brain, these hollow 3D structures will be coatedwith neurotrophic factors and immunosuppressants to promote
dendritic ingrowth and reduce inflammatory response.
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cortical recordings from the probes implanted in rat barrel cortex.

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CONTACTACKNOWLEDGEMENTS*E. Meng, tel: +1-213-821-3949; ellis.meng@usc.edu

The authors wish to thank Dr. Donghai Zhu and members of
the Biomedical Microsystems Lab for their assistance.
This work was sponsored by the Defense Advanced Research
Projects Agency (DARPA) MTO under the auspices of Dr. Jack33