3D Expandable Microwire Electrode Arrays Made of

Programmable Shape Memory Materials Ruoyu Zhao1*, Xin Liu1* , Yichen Lu1, Chi Ren2, Armaghan Mehrsa1, Takaki Komiyama2 and Duygu Kuzum1

1 Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA, 2 Neurobiology Section and Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Email: dkuzum@ucsd.edu, *These authors contributed equally

Abstract Nitinol, a biocompatible material with shape

memory effect and superelasticity, has been used in various

biomedical applications. Here we demonstrate a 3D

expandable nitinol microwire electrode array that can be

programmed to the desired shape to conform to the brain

vasculature, minimizing the vessel damage during

implantation. We developed a fabrication process for precisely

setting the shape of nitinol microwires and assembling them to

form electrode arrays. We tested our nitinol microwire array in

in vivo animal experiments and successfully demonstrated that

our array can detect single spikes as well as local field

potentials with minimum tissue and vessel damage.

I. INTRODUCTION

Implantable microelectrode arrays have been widely

employed for recording various types of neural activities in

basic neuroscience research and clinical studies. However,

chronic stability of these implantable arrays has been

significantly impeded by reactive tissue response as a result of

implantation damage. Part of the tissue response arises from the

vasculature damage in the brain. Insertion of electrodes leads to

disruption of the blood brain barrier and hemorrhages from

disrupted brain blood vessels. These hemorrhages are

specifically detrimental for chronic long-term recordings.

Bleeding from the blood vessels around the electrodes are

known to cause extensive neuronal loss [1]. As a result,

implantable array loses its ability to reliably record neural

activity over time, as observed numerous times with widely

adopted Utah arrays used in brain computer interface studies

[2]. Therefore, it is extremely important to address vascular

damage to improve the chronic reliability of implantable

microelectrodes. Novel neurotechnologies, which penetrate

into the neural tissue without puncturing blood vessels, are

particularly needed. In order to minimize the blood vessel

damage, microelectrode arrays conforming to the structure of

the brain vasculature can be built (Fig. 1). 3D vasculature of the

brain can be imaged in great detail using 2-photon microscopy

[3]. A replica of major vasculature can be constructed using

microfabrication or 3D printing techniques. Expandable 3D

microelectrodes conforming to the surrounding vasculature,

without damaging them during insertion can be developed.

However, that requires electrode materials that are

programmable to specific shapes and deformable to fit in small

volumes for implantation.

In this work, we investigate programmable microwire

electrode arrays made of a shape memory alloy, nitinol, which

is a Nickel-Titanium alloy exhibiting shape memory effect and

superelasticity (Fig. 2). At high temperature, superelasticity

allows nitinol to undergo large strain, while still able to return

to the original shape. At low temperature, nitinol can be

deformed to different shapes arbitrarily. When heated (i.e. body

temperature), shape memory effect allows it to return to its

original shape [4]. Furthermore, nitinol is biocompatible and

MRI compatible [5]. Therefore, it has already been widely used

in many different biomedical devices ranging from orthopaedic

wires and screws, bone staples of electrodes, stents, surgical

instruments, and cardiac implants [6, 7].

Here, we demonstrate nitinol microwire arrays

programmable into desired shape via current application. We

fabricated nitinol microwire electrodes with a diameter of ~30

m. We performed systematic studies to understand the effect

of current programing to shape memory effect and super-

elasticity. The electrochemical characteristics of the microwires

were characterized using impedance spectroscopy and cyclic

voltammetry. In in vivo experiments with mice, we

demonstrated successful recording of local field potentials and

single neuron spiking activity from cortical layer IV neurons.

Tissue damage analyses were used to examine the brain damage

induced by 3D expandable microelectrode implantation.

II. NITINOL MICROWIRE ELECTRODE FABRICATION

The 16-electrode microwire bundles were prepared using

-CW,

Fort Wayne Co). In order to change the cold worked wire into

super elastic condition, current annealing was done by applying

a 90 mA current through the wire for 20 s. After annealing, the

wires became straight and possessed superelasticity. A PDMS

mold with designated grooves that are 150 m wide and 150 m

deep was prepared, as shown in Fig. 3. The nitinol wires placed

in the grooves were heated up for shape setting by applying

current through joule effect. In order to find the optimal current

amplitude and duration for shape-setting, we investigated the

effect of current amplitude and duration on the bending angles.

As shown in Fig. 4, the bending angle increases towards the

target angle with higher current amplitude and duration.

However, if the amplitude and the duration are too large, the

wires overheat and lose superelasticity. Therefore, we set the

current amplitude and duration to 155 mA and 10 s to achieve

reliable shape-setting. As shown in Fig. 5, the bending angles

have small variance across different wires. After shape-setting,

4.5 m thick Parylene-C was coated on the wires as the

insulation layer. The integrity of Parylene-C insulation layer is

inspected by scanning electron microscopy (SEM) and

electrochemical characterization. Fig. 6a shows a SEM picture

978-1-7281-1987-8/18/$31.00 ©2018 IEEE 29.2.1 IEDM18-664

of the nitinol bundle. Fig. 6b shows the diameter of the

microwire before and after coating. It can be seen that the

Parylene-C layer has the desired thickness of 4.5 m. A 1 cm

long Hamilton stainless steel needle with 210 m inner

diameter was used to bundle the nitinol wires so that they were

constrained within a small space for implantation to the brain.

The Hamilton needle does not penetrate the tissue; it only

provides mechanical support for the bundle to implant

microwires to the brain with minimal damage. Parylene-C

coating was removed from the wire tips. A picture of the

microwire array is shown in Fig. 7. A 3D printed

microelectrode holder was designed to provide mechanical

support for the microwire array and to fix the PCB board with

epoxy. The nitinol/solution interface was characterized by

electrochemical impedance spectroscopy (EIS) and cyclic

voltammetry (CV). The EIS results in Fig. 8a & 8b show that

the nitinol electrode exhibits impedance values in a reasonable

range for electrophysiological recordings. The CV result in Fig.

8d shows no redox reactions at the electrode/electrolyte

interface. As shown in Fig. 8c, the mean impedance is ~1.03

M measured at 1 kHz. In order to test the 3D expansion of the

array, we 3D printed a brain vasculature model using real data

from NIH 3D print exchange database and constructed a brain

phantom by immersing it into the agarose. As shown in Fig. 9,

the nitinol array successfully penetrates and avoids the vessels.

III. IN VIVO ANIMAL EXPERIMENT

We validated the nitinol microwire bundle in in vivo animal

experiments with mice during anesthesia and wakefulness.

During the surgery, a wild-type mouse was anesthetized with

1% 2% isoflurane and a circular piece of scalp was removed to

expose the skull. After cleaning the soft tissue on top of the

bone, a head-bar was implanted with cyanoacrylate glue and

cemented with dental acrylic. A craniotomy (~1mm in

diameter) was made over the primary visual cortex. The

ground/reference screws were implanted on the cerebellum.

Fig. 10 shows the experimental setup. The nitinol bundle was

connected to a custom PCB, which was held by a custom-made

holder attached to a micromanipulator (MP-285, Sutter

Instrument). The electrodes were inserted to the visual cortex

with an angle of 45° to the horizontal plane. After the

experiment, we perfused the animal and sliced the brain to

examine the tissue damage. Compared to the intact contralateral

visual cortex without insertion, only small dents could be

observed on brain surface and minimal damage caused by

electrodes could be detected at recording site. (Fig. 11).

IV. NEURAL DATA ANALYSIS

Fig. 12a shows a typical raw electrophysiological data

recorded by one of the microelectrodes in layer IV (400 um

deep) of the mouse visual cortex during anesthesia. To

investigate the signal in frequency domain, we compute the

spectrogram using wavelet transform (Fig. 12b). It can be seen

that, during anesthesia, the local field potential (LFP) exhibits

transient oscillations in different frequency bands lasting

between 2 10 seconds. As shown in Fig. 12c & Fig. 12d, we

observed theta oscillations that have a central frequency around

7 Hz and have peak-to-peak amplitude of ~100 V. Also, as

shown in Fig. 12e & Fig. 12f, there are 12 Hz alpha band

oscillations that emerge randomly with similar amplitude as the

theta oscillation. Finally, we observed activities that resemble

the burst suppression waveforms that are commonly observed

in LFP recordings during anesthesia (Fig. 12g & Fig. 12h) [8].

The waveform consists of a large biphasic waveform, coupled

with oscillations between 5 to 15 Hz. Also, right before and

after the bursting activity, the recorded electrical signals are

flat, which is distinct from other time segments. These results

confirm that our nitinol microwire electrode array can

successfully record the LFPs of various dynamics with very low

noise and high fidelity.

Besides the anesthesia, we also investigate the neural

activities in awake state. Fig. 13a shows electrical recordings

from a representative channel. Different from anesthesia, the

electrical signals during awake state have larger amplitude.

The spectrogram in Fig. 13b shows that compared to

anesthesia, the power in almost all frequency bands increases.

Also, there are no obvious oscillations in single frequency

bands. Finally, during the awake state, we recorded high

frequency multiunit activities and single spikes, which reflect

the firing of far-away and nearby neurons respectively [9]. To

see this, we filtered the data at 500 Hz using an 8th order

Butterworth high-pass filter (Fig. 13c). Then we applied an

amplitude threshold and a time window of 2 ms to extract the

spikes. To assign different spikes to the neurons, we perform

k-means clustering on the spike data. Fig. 13d shows an

example of the clustering result from one of the channels.

Different colors label the spikes that come from different

neurons. These results show that the nitinol microwire can

detect the single spikes and multiunit activities with high

fidelity. Low noise observed in both anesthetized and awake

recordings allows probing rich dynamics exhibited by single

neurons and neuronal populations.

V. CONCLUSION

In this work, we developed a shape-programmable nitinol

microwire array that conforms to the brain vasculature to

minimize the damage to the blood vessels during implantation.

We demonstrate that our nitinol microwire bundle can reliably

record both local field potential and spiking activities in in vivo

experiments. The developed nitinol microwire bundle provides

new opportunities for vessel-damage free neural interfaces in

chronic animal research to achieve stable long-term electrical

recordings with minimum implantation damage.

ACKNOWLEDGMENTS The authors acknowledge Office of Naval Research

(N000141612531) and National Science Foundation (ECCS-1752241, ECCS-1734940) for funding.

REFERENCES [1] W. M. Grill, et al., Annu. Rev. Biomed. Eng., vol. 11, p. 1-24, 2009.

[2] V. S. Polikov, et al., J Neurosci Methods, vol. 148, p. 1-18, 2005.

[3] M. Thunemann, et al., Nat Commun, vol. 9, p. 2035, 2018.

[4] Y. Guo, et al., CIRP ANN-MANUF TECHN, vol. 62, p. 83-86, 2013.

[5] T. Duerig, et al., Mater. Sci. Eng., A, vol. 273, p. 149-160, 1999.

[6] M. Geetha, et al., Prog. Mater Sci., vol. 54, p. 397-425, 2009.

[7] A. Bose, et al., Stroke, vol. 38, p. 1531-1537, 2007.

[8] K. K. Sellers, et al., J Neurophysiol., vol. 110, p. 2739-2751, 2013.

[9] G. Buzsaki, et al., Nat Rev Neurosci, vol. 13, p. 407-20, 2012.

29.2.2IEDM18-665

Fig. 1. A schematic showing the

programmable nitinol wires penetrating to the

brain, avoiding the blood vessels.

Fig. 2. A schematic showing the super-

elasticity effect and the shape memory

effect of the nitinol alloy. Adapted from

[4].

Fig. 3. A schematic showing the method

of wire shape-setting using PDMS mold.

The inset figure shows the nitinol wires

embedded in the grooves.

Fig. 4. (a) The relationship between the bending angle and the amplitude of 10 s DC current. (b) The

relationship between the bending angle and the duration of the 140 mA DC current. Red line shows

target angle. (c) The representative shape of the wires after shape-setting using different currents.

Fig. 5. The bending angles of 30

wires after shape setting with

155 mA current for 10 s.

Fig. 6. (a)Scanning electron microscopy image shows Niti microwires

expanded from the the tip of the Hamilton needle. (b) The wire diameters

before and after coating are shown in the right diagram.

Fig. 7. (a) A photo of the device that shows Niti microwire

bundle, the microwire holder, and the custom PCB. (b) A

zoom-in picture showing the tip of the electrode bundle.

Fig. 8. (a) (b) The EIS results of all the 16 channels. (c) The impedances of all the channels measured at 1 kHz. The red line indicates

the average impedance. (d) The CV curve of one representative channel.

(a) (b)140mA

150mA

160mA

Bending

angle

(c)

500 m(a) (b) (a) (b)400 um1 cm

(a) (b) (d)(c)

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Fig. 9. A picture of the 3D printed brain

vasculature phantom with nitinol wire bundle

inserted. The wire conforms with the curvature

of blood vessels.

Fig. 10. A picture of the experimental setup,

showing the board, the nitinol bundle, and the

brain. The lower right cartoon shows the awake

and head-fixed animal during the experiment.

Fig. 11. Brain slice imaging

shows the minimal damage

caused by the nitinol

microwires. The arrow shows

penetrating position and angle.

Fig. 12 (a) Representative raw electrophysiological recordings during anesthesia. (b)

Spectrogram for the signals shown in (a). (c) Example time series of alpha oscillations

and (d) its spectrogram. (e) Example time series of theta oscillations and (f) its

spectrogram. (g) Example burst/suppression wave and (h) its spectrogram.

Fig. 13 (a) Representative raw data from

awake recordings. (b) Spectrogram for data

shown in (a). (c) High-pass filtered data

showing single spike and multi-unit

activities. (d) spike sorting results using the

data recorded by a typical channel.

Customized

PCB

Nitinol

Needle

Mouse

Brain

Head

Fixation V1

1 mm

200 m

(a)

(c)

(b)

(d)

(e) (f)

(g) (h)

(a)

(c)

(d)

(b)

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