Improving Neuron Stimulation Efficency by Altering Electrode

Geometry

A. Ghazavi

, D. Westwick

, C. Luk

, N. I. Syed

and C. Dalton

Department of Electrical and Computer Engineering, University of Calgary, Calgary, Alberta, Canada

Department of Anatomy and Cell Biology, University of Calgary, Calgary, Alberta, Canada

Keywords: Neuron-electrode Interface, Neuron Stimulation, Sealing Resistance, Finite Element Model, Micro

Electrode Array.

Abstract: Microelectrode arrays (MEA) are non-invasive tools for recording brain cell activity and have been

successfully applied to a variety of neurons. However, MEAs fail where consistent stimulation of neurons is

desired over an extended period of time. Here, a model is presented to study features that provide optimum

stimulation threshold from different sizes and shapes of electrodes. Both simulation and in vitro

experimental results suggest that star-shaped electrodes enable a threshold voltage that is 25% lower than

that of an electrode with a circular shape, and are thus considered more efficient for neuronal stimulation.

These findings are important as they will help produce more efficient microelectrode arrays for in vivo

applications such as prosthetic devices, as well as for long-term in vitro neuron stimulation for studying

neuronal networks and function.

1 INTRODUCTION

Stimulating microelectrode arrays are the basis for

neuroprosthetic devices such as cochlear and retinal

implants, bladder prostheses, upper and lower limb

prosthetics as well as treatments for neurological

disorders such as nerve regeneration electrodes, deep

brain stimulation and vagus nerve stimulation

(Cogan, 2008). Electrodes used for neuron

stimulation should be able to stimulate the neurons

for a long time period without causing neural

damage (Rutten, 2002). Efficient power

consumption of the electrode is also an important

feature to be considered in their design (Wei and

Grill, 2009). In order to optimize the neuron

stimulation to achieve physiological levels of

stimulation, it is necessary to design a more effective

neuron-electrode junction. Several models have been

used to investigate different approaches for

improving an individual neuron-electrode interface.

Investigations have considered: the effect of

complete and defect sealing on sealing resistance

and stimulus transfer; the effect of cell size on

membrane depolarization (Buitenweg et al., 1999);

the effects of neuron eccentricity; sealing gap size,

and both cell and microelectrode radius for circular

microelectrodes smaller than the cell on passive

membrane depolarization (Buitenweg et al., 2003);

the effects of anodic and catodic current stimuli on

cell excitation for a circular microelectrode larger

than the cell (Schoen and Fromherz, 2008) and the

efficiency of high-perimeter planar electrodes for

exciting axons (Wei and Grill, 2009).

In the present research, the electric field pattern

for different planar microelectrode dimensions and

shapes was investigated, in order to optimize the

electrode geometry and to obtain the largest electric

field within a cell. Our research shows that shapes

with sharp edges and longer perimeters result in

higher electric fields and sealing resistances.

2 MATERIALS AND METHODS

2.1 Experimental Methods

Neurons were experimentally stimulated by a

microelectrode array and their responses were

measured using sharp electrodes. The lowest

stimulation amplitude which caused an action

potential was compared between the different

electrode designs.

Ghazavi A., Westwick D., Luk C., Syed N. and Dalton C..

Improving Neuron Stimulation Efﬁcency by Altering Electrode Geometry.

DOI: 10.5220/0004238900510056

In Proceedings of the International Conference on Biomedical Electronics and Devices (BIODEVICES-2013), pages 51-56

ISBN: 978-989-8565-34-1

 2013 SCITEPRESS (Science and Technology Publications, Lda.)

2.1.1 Planar Electrodes

Electrolyte/SU8/Au/Cr electrodes were used in this

research. Electrodes are fabricated onto 1mm glass,

with 10nm chrome and 150nm gold (Figure 1). The

electrodes are covered with 0.5µm SU-8, which is

patterned to have holes through the SU-8 to the star

electrodes. The SU-8 layer aids physical location of

the cell. The star-shaped electrodes are made in three

different sizes with areas of approximately 280



478



and 798



and perimeters of

approximately 106µm, 148µm and 186µm (Figure

2), respectively. On each chip, there were three star

shaped electrodes, each one with a Lymnaea

stagnalis neuron, left pedal dorsal1 (LPeD1),

cultured on it.

Figure 1: Cross section of one electrode.

Figure 2: Star electrodes with LPeD1 neurons cultured on

them. The distance between electrodes is 100µm.

Figure 3: Circular electrodes with LPeD1 neuron cultured

on them.

Conventional circular electrodes, 30µm in

diameter were used for comparison purposes (Figure

3). The area and perimeter of the circular electrodes

was 707



and 94µm, respectively. Four neurons

were cultured onto four different circular electrodes.

The electrodes were set at a distance of 100µm from

each other.

2.1.2 Neurons

Neurons were extracted from isolated Lymnaea

Stagnalis brains. The cell culture process was done

according to previously published protocols as

described by Syed et al. (1999). The cells were

cultured on the electrodes which had been coated

with poly-L-Lysine one day prior to the stimulation

experiments.

2.2 Finite Element Modelling

An individual neuron-electrode interface has been

modelled using the electric current mode of

COMSOL 4.3(COMSOL Inc, USA), a Finite

Element Modelling (FEM) software package. The

transient FEM was developed in three-dimensions to

model neuronal response in the subthreshold region.

The model was meshed with 772014 and 622573

tetrahedral mesh elements for the star and circular

electrodes, respectively. Poisson equation was

solved numerically via FEM.

.   0

(1)

V the electrical potential and σ is the medium

conductivity. The model includes an insulating

surface around the glass. A falling voltage ramp with

a slope of -60mV/ms in the duration of 10ms has

been applied to the electrode. The passive response

of neurons to subthreshold voltage ramp

stimulations was compared for different electrodes.

Since the membrane as well as the sealing gap and

electrode double layer have small thicknesses

compared to the other dimensions of the model, they

have been modelled with a thickness larger than

their actual thickness and their conductivity and

permittivity have been compensated for the

difference, as described by Buitenweg et al. (1999)

and Choie and You (2012).

The level of discretization was validated by

comparing both denser and coarser meshes.

2.2.1 Microelectrode

Several models have been proposed to represent the

electrode-electrolyte impedance. There are two

processes at the interface; faradaic and non-faradaic.

In this research it has been assumed that there is no

faradaic current at the gold-extracellular interface so

the charge-transfer resistance and Warburg

impedance have not been implemented in this

model. Capacitive charging of the electrode double

layer (DL) has been assumed to be the source of

neuron stimulation. These currents are produced by

the electrode double layer which acts as a capacitor.

The pseudo capacitive resistance is assumed to be

purely capacitive so:

BIODEVICES2013-InternationalConferenceonBiomedicalElectronicsandDevices





 ;β=1 , k=1/C

(2)

In this work, the value 15µF/



as reported in

literature, has been used for electrode impedance

(Huang et al., 2004); (Yúfera et al., 2003). In reality

the electrode DL is about 2nm (Huang et al., 2004).

Since meshing very thin layers in FEM is

computationally costly, in the model a higher

thickness 0.5µm has been considered and the

difference is implemented in the permittivity.









.



(3)

2.2.2 Neuron

The neuron was simulated as a paraboloid shape

with radius 30µm and height 20µm

(height0.7*radius). Variation of the height of

neuron has a very small effect on stimulus transfer

(Buitenweg et al., 1999). Since passive membrane

properties have been assumed in the model,

capacitive and resistive properties of the membrane

are implemented in the model. Since a membrane’s

capacitance is inversely related to its thickness,

which has a constant value for animal cells

(Molleman, 2003), we have considered the

value1µF/



, as reported in other literature (Choi

and You, 2012); (Molleman, 2003); (Huang et al.,

2004); (Moulin et al., 2008); (Elia et al., 2009);

(Buitenweg et al., 2003); (Schoen and Fromherz,

2007) for membrane specific capacitance.

The resistive properties of the membrane were

represented by its conductivity. Right Pedal Dorsal1

(RPeD1) neuron’s electrophysiology and size is

almost the same as those of Left Pedal Dorsal1

(LPeD1) neuron, so the conductivity of RPeD1,

10nS (Lu and Feng, 2011), was used. The

conductance and relative permittivity for the

intracellular medium was considered to be 1.43S/m

and 80, respectively. Due to the small thickness of

the membrane, 8 nm (Huang et al., 2004), a large

number of mesh elements was required. So it has

been modelled as an interface layer between the

intracellular and extracellular media (Choi and You,

2012).









.



(4)









.



(5)

The gap between the cell and electrode is in reality

around 50nm (Schoen and Fromherz, 2008), which

was implemented as 0.5µm in the model, and then

compensated for by using a higher conductivity.









.















(6)

A geometric visualization of a neuron sitting on top

of the star-shaped electrode, as implemented in

COMSOL, is depicted in (Figure 4).

Figure 4: 3D geometry used in finite element modelling.

2.2.3 Electrolyte Bath

The values 1.65S/m and 80 were assigned to the

conductivity and relative permittivity of the

extracellular medium. It was modelled as a 60µm

diameter hemisphere. The boundary of this area was

considered as an electrical ground representing an

electrode faraway and its potential was set to zero

potential.

3 RESULTS

3.1 Passive Response under

Current-clamp

Experiments were performed with three electrodes

of each shape and size. Since falling voltage ramps

depolarize the membrane with a lower slope than is

required by rising ramps (Schoen and Fromherz,

2008), falling voltage ramps with steps of -50mV

were used for the experiments. The cells were

stimulated by the microelectrode arrays and the

intracellular response was measured using a sharp

electrode. A circular electrode with an area of

707µ



and perimeter of 94µm caused an action

potential (AP) when the stimulus exceeded -

1000mV. The small, medium and large star shaped

electrodes with perimeters of 106µm, 148µm,

186µm and areas of about 280



, 478



and

798



all caused APs with -750mV stimuli, which

is 25% less than the circular electrode. So although

the large star shaped electrode has a larger area than

the circular electrode, it can stimulate the cells using

lower voltages.

Simulation results of intracellular response of the

star-shaped electrode versus horizontal displacement

from the centre of electrode, is depicted in (Figure

5).

ImprovingNeuronStimulationEfficencybyAlteringElectrodeGeometry

Figure 5: Intracellular Response to extracellular

stimulation with falling voltage ramp of -60mv/ms and

star electrode with respect to displacement from the

centre, at times 2ms, 5ms, 7ms and 10ms.

Simulation results of the intracellular response

due to a circular electrode with the same area as the

star-shaped electrode is illustrated in (Figure 6).

Figure 6: Intracellular response to extracellular stimulation

with falling voltage ramp of -60mv/ms and circle electrode

with respect to displacement from the centre, at times 2ms,

5ms, 7ms and 10ms.

As can be seen, the star electrode, results in a

larger hyperpolarisation of the intracellular medium.

Figure 7: Electric field at different areas of the cell at the

termination of stimulus voltage ramp on star electrode.

Figure 8: Electric field at different areas of the cell at the

termination of stimulus voltage ramp on circular electrode.

Figures 7 and 8 show that the electric field is

larger in the unattached membrane for the star-

shaped electrode in comparison to the round

electrode.

3.2 Current Density Distribution on

Electrode

It has been reported that high charge density on the

electrode surface can result in cell damage when

these electrodes are used for stimulating parts of

brain tissue (McCreery et al., 1990). With the

experiments performed here it was observed that

using star shaped electrodes did not cause cell death

or visibly damage the individual cells. Figures 9 and

10 illustrate the current density distribution on the

star-shaped electrode surface at the termination of a

stimulus.

Figure 9: Current density on star electrode due to -

60mV/ms falling voltage ramp stimuli, versus

displacement from the centre of electrode at t=10ms.

Figure 10: Current density distribution on star electrode

due to -60mV/ms falling voltage ramp stimuli at t=10ms.

Figures 11 and 12 illustrate the current density

distribution on the circular electrode surface at the

termination of a stimulus.

As seen in figures 9 and 11, the star electrode

results in a spatial non-uniformity in the current

density which is almost three times that of the

circular electrode. Since the activating function is

proportional to the spatial derivative of current

BIODEVICES2013-InternationalConferenceonBiomedicalElectronicsandDevices

density, larger non-uniformity results in a larger

activating function and thus more effective

stimulation (Wei and Grill, 2009). Furthermore,

during the experiment no cell damage was observed

and the threshold voltage was reduced for the star

electrodes, as compared to the circular electrode.

Figure 11: Current density on circular electrode due to -

60mV/ms falling voltage ramp stimuli, versus

displacement from the centre of electrode at t=10ms.

Figure 12: Current density distribution on circular

electrode due to -60mV/ms falling voltage ramp stimuli at

t=10ms.

The sealing resistance obtained from FEM

ANALYSIS was calculated by dividing the

electrode voltage by the whole current on the

electrode surface while assuming that current

through the cell is negligible compared to current

through the sealing gap (Buitenweg et al., 1999).

The sealing resistance of the star electrode at 9ms

was 5GΩ while for the circular electrode it was

32.9MΩ. This shows that sealing resistance

increases by changing the electrodes shape from

circular to star.

3.3 Model Validation

The simulation results were compared with

experimental data using custom made MEAs with

various electrode geometries. The results of FEM

ANALYSIS matched well with the experimental

results. Since experimentally star-shaped electrodes

were excited at lower voltages compared to round

electrodes.

The experimental results showed that an action

potential was triggered by smaller stimulus

amplitudes when star shaped electrodes were used

instead of circular electrodes. Previous studies

(Buitenweg et al., 2003) show that smaller circular

electrodes result in higher intracellular response. The

electrode areas of two star shaped electrodes are

smaller than the circular electrode and they resulted

in a cell excitation with lower stimulus. However the

larger star electrode which had a larger area than the

circular electrode caused neuron excitation with

lower stimulus amplitudes as well.

4 CONCLUSIONS

Circular microelectrodes with smaller radius

produce a larger response to extracellular

stimulation (Buitenweg et al., 2003). Serpentine

electrodes in centimetre dimensions reduced the

threshold voltage at higher perimeters and farther

distances from the electrode (Wei and Grill, 2009).

In the present study we examined the effect of sharp

edges as well as perimeter and area on neuron

stimulation by microelectrodes. Results show that

sharp edges have a higher impact than other

geometries since the medium and large star

electrodes were excited by the same voltage. The

model result showed that using electrodes with the

same area but different perimeter and sharp edges

results in larger hyperpolarisation in the cell and a

higher current density, almost three times that of the

round electrode, at the edges. Therefore, it would be

ideal if electrodes were designed to be smaller than

the neuron being investigated and also to contain

sharp edges. Future work will investigate different

electrode geometries, both through simulation and

also via experimental study.

ACKNOWLEDGEMENTS

The authors wish to acknowledge the research grants

from the Alberta Ingenuity Fund, The Natural

Sciences and Engineering Research Council of

Canada (NSERC) and The Canadian Institute of

Health Research (CIHR), Regenerative Medicine

and Nanomedicine Program RMF 82496.

We also wish to thank the Advanced

Micro/Nanosystems Integration Facility at the

University of Calgary for fabricating the devices.

ImprovingNeuronStimulationEfficencybyAlteringElectrodeGeometry

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BIODEVICES2013-InternationalConferenceonBiomedicalElectronicsandDevices