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Nanostructured gold microelectrodes for extracellular recording from

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Nanotechnology 22 (2011) 265104 (7pp) doi:10.1088/0957-4484/22/26/265104

Nanostructured gold microelectrodes for

extracellular recording from electrogenic
cells
D Brüggemann1, B Wolfrum, V Maybeck, Y Mourzina,
M Jansen and A Offenhäusser
Institute of Complex Systems and Peter Grünberg Institute: Bioelectronics (ICS8/PGI8),
Forschungszentrum Jülich GmbH, Leo-Brandt-Straße, 52428 Jülich, Germany
and
Jülich–Aachen Research Alliance—Fundamental of Future Information Technology
(JARA-FIT), Germany

E-mail: a.offenhaeusser@fz-juelich.de

Received 18 January 2011

Published 18 May 2011
Online at stacks.iop.org/Nano/22/265104

Abstract
We present a new biocompatible nanostructured microelectrode array for extracellular signal
recording from electrogenic cells. Microfabrication techniques were combined with a
template-assisted approach using nanoporous aluminum oxide to develop gold nanopillar
electrodes. The nanopillars were approximately 300–400 nm high and had a diameter of 60 nm.
Thus, they yielded a higher surface area of the electrodes resulting in a decreased impedance
compared to planar electrodes. The interaction between the large-scale gold nanopillar arrays
and cardiac muscle cells (HL-1) was investigated via focused ion beam milling. In the resulting
cross-sections we observed a tight coupling between the HL-1 cells and the gold nanostructures.
However, the cell membranes did not bend into the cleft between adjacent nanopillars due to the
high pillar density. We performed extracellular potential recordings from HL-1 cells with the
nanostructured microelectrode arrays. The maximal amplitudes recorded with the nanopillar
electrodes were up to 100% higher than those recorded with planar gold electrodes. Increasing
the aspect ratio of the gold nanopillars and changing the geometrical layout can further enhance
the signal quality in the future.
(Some figures in this article are in colour only in the electronic version)

1. Introduction to-noise ratio (Isik et al 2005). Two major factors influence

Functional coupling of cellular networks to chip-based
devices may impact various biomedical applications, e.g. the
development of neural prostheses, drug delivery systems, or
tissue engineering. Currently, planar microelectrode arrays
(MEAs) are state-of-the-art for extracellular recording of
electrical activity on a chip. The main disadvantage of flat
electrodes is their low signal-to-noise ratio (Hai et al 2010).
During extracellular signal recording, the interface between
the cell and the electrode, and thus the electrode geometry,
plays a significant role in detecting signals with a high signal-
1 Present address: CRANN—The Naughton Institute, School of Physics,
Trinity College Dublin, Dublin 2, Ireland.
the cell–chip coupling: one is the cell adhesion, and the
other is the input impedance of the electronic interface. The
resistance of the sealing gap between the cell and the electrode
directly influences the signal, giving large signal amplitudes for
strongly sealed electrode junctions (Rutten 2002). On the other
hand, a large input impedance, as expected for small micro- or
nanoelectrodes, can significantly lower the signal quality.
Standard materials that are currently used as microelec-
trodes for bioelectronic applications include gold, platinum,
and indium tin oxide (ITO) (Taketani and Baudry 2006, Kucera
et al 2000). Planar electrode materials, for example untreated
gold or platinum, show high impedances around 1 k cm−2
at 10 Hz which lower the amplitudes of cell recordings in
small electrode configurations. To date, different porous

0957-4484/11/265104+07$33.00 1 © 2011 IOP Publishing Ltd Printed in the UK & the USA
Nanotechnology 22 (2011) 265104
materials have already been implemented into microelectrode
technology to improve the signal quality. For example, the
enhanced surface areas of porous structures such as spongy
platinum black or Ti3 N4 lead to a reduced electrode impedance
(Pine 1980, Regehr et al 1989). Despite their good electronic
properties porous electrode materials also show problems
during signal recording. They are often blocked with proteins
used as surface modification in cell culture. Furthermore,
porous structures show mechanical instabilities since they
detach during cell cultivation or cleaning (Taketani and Baudry
2006). These disadvantages led to the development of different
microstructured tip electrodes to avoid layers of dead cells and
to enhance the electrode surface (Thiébaud et al 1997, Isik et al
2005, Heuschkel et al 2002, Nam et al 2006). The electrode
modifications enabled signal recording and cell stimulation
from various tissue slices. For the detection of signals from sin-
gle cells in networks, a miniaturization of the microelectrodes
toward nanoelectrodes is now of great importance. Recently,
a novel microelectrode modification method was presented for
neural electrode engineering with gold nanoflakes (Kim et al
2010). With these nanoflake-modified MEAs an impedance
reduction was observed, and in vitro recording and stimulation
of cultured hippocampal neurons was demonstrated. Besides
the lowering of the electrode impedance, the nanoflakes also
improved the cell–chip coupling. Other approaches to modify
MEAs for improved cell recordings include patterning with
nanostructures such as vertically aligned carbon nanotubes
(CNTs) or CNT meshes (Wang et al 2006, Nguyen-Vu et al
2006, Pancrazio 2008, Gabay et al 2007, Galvan-Garcia et al
2007, Yu et al 2007, de Asis et al 2010), silicon nanowires
(SiNWs) (Shalek et al 2010, Kim et al 2007) or metallic
nanorods (Zhou et al 2009). Some techniques even aim at
sticking the nanostructures through the membrane without
damaging the cell to achieve optimal coupling conditions at the
interface (Shalek et al 2010, Kim et al 2007, McKnight et al
2004, Verma and Melosh 2010, Almquist and Melosh 2010).
A tight coupling between the cell membrane and the
recording device leads to an increase of the voltage at the
cell–substrate interface so that small amplitude signals from
biological systems can be detected (Fromherz et al 1991, Egert
et al 1998, Heuschkel et al 2002, Taketani and Baudry 2006,
Joye et al 2009). An interesting approach for improving the
cell–chip coupling and thus enhancing the signal-to-noise ratio
of neuro–electronic hybrid systems was recently presented by
Hai et al (2009a, 2009b). They reported on the fabrication of
spine-shaped gold protrusions to enhance the electrode surface.
The adherence and electrical coupling of the neurons were
improved when growing on the gold spines. The cleft between
the neuronal cell membrane and the gold microstructures
was reduced, and the neurons even engulfed the protrusions,
leading to field potentials that were significantly larger than
the signals from flat electrodes.
A new approach for chip-based electrode modification and
miniaturization is presented in this work. We report on the
fabrication of gold nanopillar arrays on MEAs using a top-layer
template of nanoporous aluminum oxide. Nanoporous alumina
templates can be produced via self-assembly (Masuda and
Fukuda 1995). This template material is widely used for the
2
D Brüggemann et al
production of metal nanowires (Sander and Tan 2003, Wolfrum
et al 2006, Schröper et al 2008, Zhou et al 2009), polymer
nanostructures (Xiao et al 2007), semiconducting nanotubes
(Dresselhaus et al 2003, Mitchell et al 2002), carbon nanotubes
(Maschmann et al 2006), and composite nanostructures (Lee
et al 2005, Shingubara 2003). The formation, and resulting
geometry, of the nanopores was thoroughly characterized for
Al foils (Masuda and Fukuda 1995, Masuda et al 1997, 1998,
Nielsch et al 2002) and aluminum films on silicon substrates
(Sulka and Stepniowski 2009). In our approach, we use
the nanoporous templates to structure the metal electrodes of
microelectronic circuits on silicon substrates. Subsequently,
we investigate the signal recordings with the nanopillar-
modified electrodes from cardiac-like muscle cells.
2. Experimental details
2.1. Fabrication of metal electrode arrays
P-doped silicon wafers with a (100) orientation (Si-Mat,
Landsberg, Germany) served as substrates for the production
of planar gold MEAs. They were oxidized in a diffusion
oven of type TS-6304 (Tempress Systems Ing, Heerde, NL)
to obtain a top layer of 1500 nm of SiO2 . An adhesion layer of
10 nm of titanium was deposited onto the oxide in a sputter
system ZH 620 (Emerald Technology Ventures AG, Zürich
Switzerland), followed by 200 nm of gold and a second layer
of 10 nm of titanium. For photolithographic structuring of
the metal layers, the positive resist AZ 6612 (MicroChemicals
GmbH Ulm, Germany) and a mask-aligner MA 6 (Süss
MicroTec AG, Garching, Germany) were used. Afterward,
the metal layer was etched via ion beam etching with argon
in an Ionfab 300 Plus system (Oxford Instruments GmbH,
Wiesbaden, Germany) to obtain prestructured conductive
paths. A passivation layer of 300 nm of SiO2 , 200 nm of Si3 N4
and 300 nm of SiO2 (ONO stack) was then deposited onto the
wafer via plasma enhanced chemical vapor deposition (Surface
Technology Systems, STS, Newport, UK). In a second
photolithographic step the ONO stack was structured using
the photoresist AZ 1518 (MicroChemicals). The electrode
areas of the conductive paths were opened via reactive ion
etching. SiO2 was removed using CF4 and CHF3 . For opening
the Si3 N4 we employed CF4 , O2 and CHF3 . The top Ti
layer was also removed in this process. Finally, the gold
MEA wafers were coated with 800 nm of aluminum from an
electron beam evaporation system BAK640 (Unaxis GmbH,
Hanau, Germany) and were transferred out of the clean room
to perform the nanostructuring process (see figure 1).
2.2. Nanostructuring process
A custom-built cell made out of polymethylmethacrylate was
used for the anodization of the top aluminum layer. The wafers
with the gold MEAs were cut into single chips with a size of
11 × 11 mm2 to fit into this cell. The anodization bath consisted
of 0.3 M oxalic acid (Merck KGaA, Darmstadt, Germany). The
chip with the top aluminum film was fixed in the cell and served
as the anode. A platinum sheet of larger surface area than the
exposed alumina surface was used as a cathode. A potential
Nanotechnology 22 (2011) 265104
Figure 1. Fabrication of gold nanopillars on microelectrode arrays.
1. Aluminum was deposited onto the MEAs via e-beam evaporation.
2. Anodization in 0.3 M oxalic acid yielded self-assembled
nanopores of Al2 O3 . Afterward, the barrier layer of the pore bottom
was removed in 5% H3 PO4 . 3. Electrochemical filling of the pores
was performed in a K[Au(CN)2 ] bath at 60 ◦ C for 120–130 s. 4.
Finally, the Al2 O3 template was removed in 20% KOH to obtain
free-standing gold nanopillars. Their height was between 300 and
400 nm, and they were approximately 60 nm in diameter.
difference of 40 V was applied between the chip and the
counter electrode resulting in the formation of a nanoporous
aluminum oxide film. During the anodization the electrodes in
the middle of the MEA chip as well as the outer bond pads
were in direct contact with the aluminum layer. When the
nanopores reached the gold electrodes an increasing current
indicated complete anodization. A low-resistance contact of
the microelectrodes to the power supply was maintained even
after aluminum oxide formation via the feed lines and the
outer bond pads. Subsequently, the pores were widened in 5%
phosphoric acid (Merck KGaA) for 45 min, and the remaining
bottom barrier layer was removed to achieve better contact with
the underlying gold electrodes.
After formation of the alumina template, gold was
electrochemically deposited in the nanopores connecting to the
3
D Brüggemann et al
microelectrodes. The electrochemical deposition was carried
out in the galvanization solution Pur-A-Gold with K[Au(CN)2 ]
from Enthone GmbH (Langenfeld, Germany) at a final gold
concentration of 10 g l−1 and a pH value of 5.8 at 60 ◦ C. The
current density for electrodeposition was set to 6 mA cm−2
at an average voltage of 1.7 V. To grow nanopillars with an
average height of 300–400 nm the galvanization time was
between 120 and 130 s. Subsequently, the alumina template
was removed by soaking the samples in 20% KOH (Merck
KGaA) at room temperature for approximately 1 h. The free-
standing gold nanopillar arrays on the microelectrodes were
analyzed via scanning electron microscopy (SEM) using a
Gemini 1550 VP device (Carl Zeiss, Jena, Germany).
2.3. Chip encapsulation and cell culture
Finally, the chips were mounted onto carriers using flip
chip assembly. For insulation of the carriers from the cells
and the cell culture medium, the chips were encapsulated
with polydimethylsiloxane (PDMS) 96-083 (Dow Corning
Corporation, Midland, USA). Before the cultivation of the
cardiomyocyte-like cell line HL-1 (Claycomb et al 1998) on
the nanostructured gold MEAs, the chips were cleaned in a
flow cell with ultrapure water for 4 h. After drying with
nitrogen the samples were activated in oxygen plasma (Diener
electronic GmbH & Co. KG, Nagold, Germany) and were
transferred to a sterile bench where they were sterilized with
UV light for 1 h. Subsequently, the surface of the chips was
coated with fibronectin at a concentration of 1 ml in 200 ml
of 0.02% Bacto TM Gelatin (Fisher Scientific). The samples
were incubated in this solution for 1 h at room temperature.
Afterward, the cells were seeded in Claycombs Media and
cultured at 37◦ 5% CO2 in a humidified incubator.
2.4. Impedance spectroscopy and recording of extracellular
signals
Electrochemical analysis of the large-scale gold nanopillar
arrays was carried out via impedance spectroscopy in 0.15 M
NaCl (Sigma). In a three-electrode arrangement with a
platinum wire and a Ag/AgCl (3 M KCl) electrode we recorded
impedance spectra using the impedance analyzer Solartron
1260 (Solartron Analytical, UK). The amplitude of the applied
AC voltage was 10 mV.
At day in vitro 4 (DIV 4) signal recording from the HL-1
cells was performed with an MEA amplifier system designed
at our institute (Krause et al 2000) and operated using the
software MED 64 conductor™ (KF Technology srl, Rome,
Italy). A chlorinated silver wire was used as a reference
electrode. On average three different cultures of HL-1 cells
with one or two nanostructured and planar chips each were
analyzed for the respective electrode types. Thereby, the
electrode diameters ranged from 8 to 20 μm. Action potentials
were recorded from 64 electrodes per chip and averaged
afterward to obtain an average action potential per chip.
2.5. Microscopic techniques
Live–dead staining was performed using an Axio Imager
Z.1 Apotome (Carl Zeiss GmbH, Oberkochen, Germany).
Nanotechnology 22 (2011) 265104
Figure 2. Impedance spectra of large-scale arrays of gold nanopillars
and planar gold references with a size of 0.35 cm2 . The spectra were
measured in 0.15 M NaCl.
The fluorescent dye for staining live cells was calcein
(Sigma). 1 mM calcein was diluted in a solution of
1× Dulbecco’s Phosphate Buffered Saline solution (DPBS,
Invitrogen, Karlsruhe, Germany). Dead cells were stained
with 2 mM of ethidium homodimer-1 (EthD-1, Invitrogen)
in 1× DPBS. During the staining procedure live cells
are distinguished by green fluorescence generated by the
enzymatic hydrolysis of calcein. In dead cells the cell
membrane is damaged so that EthD-1 can enter, resulting
in red fluorescence from nucleic acid staining. To evaluate
the interface between the gold nanopillars and the different
electrogenic cell types, cross-sections were prepared using
a focused ion beam (FIB). Therefore, we used large-scale
arrays of gold nanopillars with comparable geometries to the
pillars produced on the MEAs. The SEM analysis of the
nanostructure–cell interfaces was carried out with a Zeiss
Gemini 1550 device. To this end, the cells were fixed on the
gold nanostructures with 3.5% glutaraldehyde (Agar Scientific
Ltd, Essex, UK).
3. Results and discussion
We employed nanoporous alumina templates to fabricate
biocompatible chip-based gold nanopillars with reproducible
geometries. The resulting nanopillars were approximately
300–400 nm high and had a diameter of 60 nm. Our aim was to
Figure 3. FIB cross-section of an HL-1 cell at DIV 4 grown on a macroscopic gold nanopillar array. (a) Cross-section through a whole HL-1
cell on gold nanopillars. (b) Magnification of the cell–nanopillar interface.
4
D Brüggemann et al
decrease the electrode impedance by modifying the electrode
surface with the gold nanopillars. In a first experiment
with macroscopic electrodes we investigated the difference in
impedance between nanostructured and planar gold surfaces.
For this purpose, the nanopillars were fabricated on planar gold
with an electrochemically accessible surface area of 0.35 cm2 .
Figure 2 shows a comparison of the impedance spectra for
the two macroscopic electrode systems measured in 0.15 M
NaCl. It can be seen that the impedance of the nanostructured
gold electrodes is significantly reduced as expected due to the
larger surface area (Schröper et al 2008, Zhou et al 2009,
Kim et al 2010). Thus, gold nanopillars offer a promising
modification method to reduce the impedance of existing
planar electrode designs. These large-scale surfaces with gold
nanopillars were chosen for impedance spectroscopy because
the impedance change cannot be measured reliably with MEAs
due to the capacitive influences of the feed lines on the chip and
because of possible passivation defects. Particularly for very
small electrode diameters the measurement of the electrode
impedance is superposed by the parasitic effects of the feed
lines and bond pads on the MEA chips.
In a next step, we investigated the growth of HL-1
cells on these macroscopic gold nanopillar surfaces to assess
biocompatibility and to get information on the cell–substrate
junction. On DIV 4, a layer of confluent HL-1 cells covered
the nanopillars. Figure 3 shows an FIB cross-section of an
HL-1 cell which was grown on gold nanopillars and fixed
afterward. We can see that the cell adhered well to the gold
nanostructures. As illustrated in figure 3, the membrane of
the HL-1 cells followed the nanotopography, but it did not
bend down to the bottom of the space between the pillars.
However, the highest pillars were in close contact with the
cell membrane almost reaching into it. For the lowest pillars
the distance between the cell membrane and the pillar tip
was 100 nm. This tight interface between the HL-1 cells
and the gold nanopillars suggested strong electrical coupling
between the HL-1 cells and the nanostructures. Nevertheless,
neither bending of the cell membrane around the nanopillars
nor incorporation of the pillars into the cell membrane was
observed.
After the initial impedance and biocompatibility studies
of the macroscopic nanopillar arrays, we transferred the
nanostructuring process to gold microelectrode arrays to
Nanotechnology 22 (2011) 265104 D Brüggemann et al

Figure 4. (a) SEM image of a microelectrode modified with gold nanopillars. The nanopillars had an average height of 300–400 nm and were
approximately 60 nm in diameter. (b) Live–dead staining of HL-1 cells on nanostructured gold MEAs with calcein and EthD-1. The red
arrows indicate where the nanostructured electrodes are situated beneath the cell layer. (c), (d) Optical light microscopy images of cultured
HL-1 cells on gold microelectrode arrays with a diameter of 15 μm at DIV 4. The electrodes with gold nanopillars in figure (c) appear black,
whereas the planar electrodes in (d) are yellow.

enhance the surface area of the microscopic metal electrodes.
The resulting nanostructured MEAs can be seen in figure 4(a).
In the center of the electrode a dense growth of nanopillars was
observed. However, at the outer edge of the planar electrode no
pillars were grown. This process-related effect occurred for all
electrodes but it is worth noting that for the smallest electrodes
(8 μm diameter) the result was that only about 20–30%
of the total electrode surface was covered with nanopillars.
We believe that this effect is caused by the inhomogeneous
coverage of the passivated microelectrodes. The Al film only
adheres tightly to the inner part of the electrodes because of
the height difference near the surrounding passivation layer.
Hence, during the anodization, the nanopores can only reach
the bottom of the electrode in the center of the circle so that
only in this area can the pores be filled with gold.
In general, the nanostructuring process was more
challenging on microelectrodes than on planar gold surfaces
due to the topography of the passivation layer, the electrode
areas, and the feed lines. The different materials and the
topography of the chips also led to unequal etch rates, e.g. at
corners of the passivation. Furthermore, the anodization
parameters had to be adjusted according to the underlying
microelectronic circuits to avoid a delamination of the
aluminum film due to inappropriately high voltages. The
presented process yielded stable nanostructures that could be
used for repetitive measurements, although mechanical forces
due to intensive cleaning can induce bending of the nanopillars.
In preparation for the signal recording, the nanostructured
and planar microelectrodes were coated with fibronectin which
yielded confluent layers of HL-1 cells, as can be seen in
figures 4(c) and (d). In the light microscopy image in
figure 4(c) the electrodes appear brown/black due to the gold
nanopillars at the surface whereas the planar gold electrodes
shown in figure 4(d) are yellow. Live–dead staining with
calcein and EthD-1 of the on-chip HL-1 cultures showed
vital cell growth throughout all measurements, as can be seen
exemplarily in figure 4(b).
Signal recordings from HL-1 cells were performed at DIV
4 with planar and nanopillar-modified MEAs. To reduce the
effect of cell culture quality on the comparison of the different
electrode types, we always plated cells on planar and pillar
electrodes in the same cell culture run. Action potentials were
recorded repeatedly from the different HL-1 cultures for all
the different electrode arrays. Figure 5 shows an exemplary
sequence of action potentials and a single action potential
recorded with a nanostructured gold electrode. The number
of channels showing action potentials depended on the density
of the HL-1 cell culture. For very dense cell cultures all 64

5
Nanotechnology 22 (2011) 265104 D Brüggemann et al

Figure 5. Extracellular recordings of HL-1 cells at DIV 4 using a nanostructured gold electrode (20 μm diameter). The signal has been
inverted after recording. (a) Train of action potentials. (b) Single action potential starting with a slight dip due to the initial depolarization of
the cell and followed by the spike caused by the inward sodium current into the cell.

Table 1. The table summarizes the comparison of the maximal cell coupling, i.e. the seal resistance between the cell
peak-to-peak amplitudes of action potentials and the noise levels membrane and the electrode, determines the extracellular
recorded with nanostructaured and planar MEAs. About 10
potential at the junction and the interface impedance of the
successive action potentials were averaged per electrode.
electrode material can strongly influence the signal quality.
Maximal Furthermore, the input impedance of the amplifier system and
Electrode Electrode peak-to-peak Rms noise
the leak resistance of the feed lines on the chip affect signal
diameter (μm) type amplitude (mV) (μV)
recordings. In this work, we addressed the improvement
10 Planar 0.40 ± 0.01 7. 0 of the interface impedance by enhancing the surface area
10 Pillar 0.83 ± 0.02 6. 6
20 Planar 0.92 ± 0.03 6. 5 due to the nanostructuring process. Although the impedance
20 Pillar 1.50 ± 0.02 6. 7 reduction was evident, as shown in figure 2, this effect is
less pronounced compared to other electrode modification
methods. For example, impedance reduction factors between
15 and 23 were reported using various CNT coated electrodes
electrodes exhibited cell activity. The resulting signals varied (Chen et al 2010, Nguyen-Vu et al 2006, Keefer et al 2008). In
strongly with regard to their shape, amplitude, and frequency. principle, similar or even higher impedance reduction values
Variability in the chip fabrication as well as differences in cell can also be obtained using nanostructured metal electrodes
fitness, adhesion, and the exact location of a cell with respect (Zhou et al 2009, Kim et al 2010). Nevertheless, the data in
to the recording electrode influenced the signal transfer to the table 1 show that even for electrodes as small as 10 μm the
chip. We assume that the variability in the recorded signals is impedance reduction has almost no effect on the noise level of
dominated by these features. our recorded traces. This suggests that in our setup we are not
To characterize the amplitude response for each electrode operating at the Johnson noise limit of the impedance at the
type we used the highest average peak-to-peak action potential, electrode–electrolyte interface.
which should represent signals under the best cell culture
The observed improvement in maximal amplitudes of the
conditions (see table 1).
cell signals is either due to an increased junction resistance or
The corresponding rms noise of these traces was
calculated in the intervals from 300 to 200 ms before the peak a better ratio of leak to electrode impedance. In principle,
of each action potential. Similar noise levels were recorded in the aspect of impedance reduction is advantageous for very
the literature involving nanostructured electrode systems such small electrodes, where the signal quality is mainly limited
as microelectrodes modified with gold nanoflakes (3.5 μV, by the high impedance. However, to efficiently transfer our
Kim et al 2010), CNT electrodes (7 μV, Gabay et al 2007) process to the nanostructuring of sub-10 μm electrodes it has
or carbon nanofiber electrodes (17 μV noise, Yu et al 2007). to be adjusted in such a way that the pillar coverage extends
However, a direct comparison is difficult since the noise is also to the outer rim of the electrodes. For larger electrode
influenced by the electrode size and the electronic setup for diameters, the impedance of the planar surfaces is already
different experiments. In our experiments the structure of quite low. In the case where the impedance of the electrode
the electrode had only a minor effect on the recorded noise. is already significantly lower than the leak impedance of the
Nevertheless, the maximal amplitudes were increased for the feed lines and the load impedance of the electronic system, a
nanostructured MEAs by up to 100%. further reduction of the electrode impedance due to electrode
The quality of the signals recorded via extracellular modifications will have no significant effect on the signal
on-chip measurements depends on different parameters. The amplitude.

6
Nanotechnology 22 (2011) 265104
4. Conclusions and outlook
In summary, we have presented a new biocompatible
nanostructured microelectrode array for signal recording from
electrogenic cells. The gold nanopillars provide a method
for lowering the electrode impedance without altering the
chemical properties of the material itself. Thus, surface
modifications of the chemically and mechanically stable gold
nanostructures via thiol coupling remain possible. Our first
successful signal recordings from HL-1 cells showed an
improvement of the signal-to-noise ratio on MEAs modified
with gold nanopillar arrays compared to planar gold MEAs.
In future studies, MEAs can also be modified with
other nanostructured metals, e.g. with platinum. Extracellular
recording experiments with nanostructured MEAs could also
be performed with primary neurons for a better understanding
of signal transduction in neuronal networks. To further
improve the signal quality during recording, we suggest
enhancing the aspect ratio of the gold nanopillars on
the electrodes. If a good seal can be achieved with
higher nanopillar MEAs, it might be possible to stick the
nanostructures directly into the cell for optimized recording
(Verma and Melosh 2010) or for targeted molecular delivery
(Shalek et al 2010, McKnight et al 2003, 2004). This would
enable us to perform on-chip intracellular experiments. At
the same time, further electrode miniaturization is possible
if higher nanostructures are used for electrode modification.
Furthermore, a lower pillar density could lead to better sealing
of the structures due to enhanced adhesion of the cells.
Acknowledgments
This project was financially supported by the Studienstiftung
des deutschen Volkes. Peter Holik from the Forschungszen-
trum Caesar, Bonn, is gratefully acknowledged for processing
the microelectrode arrays. Angelika Sehrbrock from the
Forschungszentrum Caesar, Bonn, contributed to this work in
performing cross-sectional FIB analysis.
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