1 .pdf

À propos / Télécharger Aperçu
Nom original: 1.pdf
Titre: research 1..6

Ce document au format PDF 1.5 a été généré par Arbortext Advanced Print Publisher 10.0.1465/W Unicode / PDF-XChange Viewer [Version: 2.0 (Build 51.0) (May 13 2010; 20:25:23)], et a été envoyé sur fichier-pdf.fr le 14/06/2015 à 14:32, depuis l'adresse IP 86.249.x.x. La présente page de téléchargement du fichier a été vue 682 fois.
Taille du document: 1.5 Mo (6 pages).
Confidentialité: fichier public

Aperçu du document


On Chip Guidance and Recording of Cardiomyocytes with 3D
Mushroom-Shaped Electrodes
Francesca Santoro, Jan Schnitker, Gregory Panaitov, and Andreas Offenhaü sser*
Institute of Bioelectronics ICS-8/PGI-8, Forschungszentrum Jülich D-52425 Jülich, Germany
ABSTRACT: The quality of the recording and stimulation
capabilities of multielectrode arrays (MEAs) substantially
depends on the interface properties and the coupling of the
cell with the underlying electrode area. The purpose of this
work was the investigation of a three-dimensional nanointerface, enabling simultaneous guidance and recording of
electrogenic cells (HL-1) by utilizing nanostructures with a
mushroom shape on MEAs.

KEYWORDS: Cell guidance, HL-1 cells, multielectrode array, 3D electrodes, cell−electrode interface


in influencing cell properties such as morphological and
physiological changes due to the interaction of the cell with
modified surfaces.20,21 It is biologically not completely
understood how cells interact with different kinds of 3D
structures, although there is a good indication that the actin is
the major cellular component for the cell−chip interaction by
forming a ring-shape morphology around the micro- and
nanostructures.22 Furthermore, shaping the 3D microstructures
using a biomimetic design has turned out to be a successful
approach for applications with neuronal cells as shown in ref
23. Moreover, Hai et al. recently showed24 how the interspine
space between 3D microspines in an array configuration
influences the outgrowth of Aplysia californica neurons:
matrices with interspine spaces of 4 and 8 μm exhibited a
major influence on the neurites outgrowth in contrast to ones
with a higher interspace. A similar approach was investigated,
where primary cortical neurons showed preferential outgrowth
when plated on gold mushroom-shaped spines functionalized
with amino-terminated self-assembled monolayers (SAM).23
To create well-defined patterns of cells on MEAs, many
methods have been proposed in the last years. Protein
patterning was one of the first techniques used for guidance
with defined geometries and patterns on a substrate using
microcontact printing25,26 or with lithography methods.27 In
these cases, the patterned protein is recognized by the receptors
of the cells that are responsible for the cell−extracellular matrix
boundary.28,29 The major limitation of these techniques is that
the protein pattern is restricted to two dimensions, since the
thickness of the protein layer is negligible compared with the

ultielectrode arrays (MEAs) have been largely used for
characterizing cellular networks, especially for the
investigation of electrical active cells.1−3 In the recent years,
we continuously improved these devices regarding their
interface properties and consequently allowing the extracellular
recording of action potentials and electrical and optical
stimulation.4−8 A crucial point for the recording of extracellular
signals is the contact between the cell membrane and the active
part of the device: a tight cell−electrode interface can provide
transmission of the electrical signal without significant
dissipation.9,10 Furthermore, it is of great interest to guide
cells on MEAs to allocate cells on the electrodes and create
defined cell patterns for understanding the signal propagation
between cells. State of the art MEA and field-effect-transistor
(FET) biosensors are adapted more toward three-dimensional
(3D) microstructures,11 and it was shown that the interaction
between the cell and an active device could be greatly improved
by means of nanostructures such as metal nanopillars,12 carboncoated electrodes13,14 or microspines,11,15,16 and silicon nanowires,17 making these devices only suitable for physiological
investigations by the reduction of the cleft between sensor and
cell. It was shown that gold microspines can be engulfed by a
cell membrane and not only increasing the effective contact
area but also providing a high degree of coupling for the
extracellular measurement with such electrodes.18
Yet the interface is not the only challenge for the cells being
coupled with an electronic device. The topography and
electrochemistry of the surface are just two examples of the
properties of the materials involved at the interface; it still
remains a challenge to improve the adhesion of very soft cells
with a Young’s modulus in the kilopascal regime19 onto a rigid,
inorganic material with a stiffness of MPa to GPa. The
topographical shape and its chemical properties have a key role
© XXXX American Chemical Society

Received: August 2, 2013
Revised: September 19, 2013


dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Nano Letters


Figure 1. (A) Scanning electron microscopy (SEM) image of a 3D 64-electrode array (scale bar 500 μm); (B) nanopillar electrodes with guide lines
on the passivation layer (scale bar 20 μm); (C) silicon substrate with pattern of gold nanopillars for guidance tests (scale bar 200 μm); (D) single
square design with nodes connected by 200 μm lines (scale bar 50 μm).

length and the width of the pattern. As mentioned before, 2D
guidance is driven by a receptor-mediated mechanism based on
extracellular matrix recognition; it was proposed in the recent
years to additionally create micro-nano patterning on substrates
to induce cell proliferation, alignment, and stretching.30−32
In this Letter we report about the possibility to use 3D
nanostructures for coupling cardiomyocyte-like cells with our
recording device. In particular, we investigated how one can
combine cell guidance and extracellular recordings of cardiac
cells on a chip at the same time. Therefore, we studied the
effect of cell guidance on mushroom-shaped 3D gold
nanostructures which were fabricated onto a MEA chip for
extracellular recordings.
In this work, we used a MEA processed as shown in ref 33.
The electrode layout was adapted from ref 34, while we
increased the overall chip size to 24 × 24 mm2 to simplify the
flip-chip encapsulation to a top contact chip. For the fabrication
of the gold nanostructures we refer to ref 23. Briefly, a thin gold
film was deposited on the substrate, which was then covered by
a poly(methyl methacrylate) (PMMA) e-beam resist (Allresist
GmbH, Berlin, Germany) with a thickness of about 1 μm. The
apertures around 500 nm have been exposed by means of ebeam lithography. Consequently, the openings were filled by
electroplated gold using the sputtered gold film as a
background electrode. The gold nanostructures were electroplated on top of the planar MEA gold electrode with a diameter
of 8 μm as shown in Figure 1A−B. Additionally, gold lines with
a length of 180 μm have been fabricated between adjacent
electrodes on the top of the passivation layer without shortcircuiting the electrodes (Figure 1B). The width of the lines
was about 15 μm in the case of two parallel lines of pillar
featuring a 10 μm pitch and was scaled up to six parallel lines
when the smallest pitch was fabricated. In the next processing
step all of the gold strip-lines were electrically short-circuited by
a 50 nm aluminum layer. This circuit was electrically connected
to the MEA electrodes to galvanize simultaneously the cell
guiding mushroom lines and the electrode gold nanostructures

of the MEA itself. Finally, the resist was removed, and the
aluminum shorts were etched with an aluminum wet etchant
(ANPE80/5/5/10, Microresist Technology, Berlin, Germany).
Adopting these parameters, we were able to fabricate
mushrooms with a diameter of about 500 nm, a stalk height
of about 1 μm, and a cap height of 200 nm. The overall
effective surface area of an individual pillar was about 4.5−10
μm2, depending on the surface roughness of the cap, resulting
in a total electrode surface of about 77−115 μm2 in case of the
8 μm (diameter) electrodes for electrophysiological measurements. We determined the equivalent capacitance values of
about 30 pF per electrode with the help of impedance
spectroscopy. In addition to the MEAs with cell-guiding
nanostructures, we fabricated 64 gold pillar node containing
samples on silicon oxide for the optimization of spine
interspacing in cell guide lines (Figure 1C−D). The pitch
between nanopillars was varied in the range from 2 to 10 μm.
To cultivate cardiomyocyte-like cell line HL-1,35 the Si test
samples and the MEAs were cleaned in flowing ultrapure water
for 2 h and then sterilized for 30 min with UV light. After the
sterilization, the surface of the substrates was coated with
fibronectin at a concentration of 1 mL in 200 μL of 0.02%
Bacto TM Gelatin (Fisher Scientific) for an incubation time of
1 h. Confluent HL-1 cells in a T-25 flask were treated with
0.025% trypsin/EDTA, suspended in 5 mL of Claycomb
medium, and centrifuged for 5 min at 1700 rpm. The pellet was
then resuspended in 3 mL of medium, and 30 μL was plated on
the substrates. After 15 min 1 mL of medium was added, and
the substrates were incubated for 3 days until the cells formed a
confluent monolayer on the lines and started to contract. The
living cells on the silicon substrates were stained with 1 mM
calcein AM (Invitrogen) and 1 mM ethidium homodimer in
phosphate-buffered saline (PBS) solution (137 mM NaCl, 2.7
mM KCl, 8 mM Na2HPO4, 1.8 mM KH2PO4), and the image
acquisition was performed using an Axio Imager Z.1 (Carl Zeiss
AG, Oberkochen, Germany).

dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Nano Letters


Figure 2. (A) HL-1 cell on Si test sample stained with 1 mM calcein AM and 1 mM ethidium homodimer (scale bar 200 μm); (B) 87% guided cells
on Si test sample (i) and 96% guided cells (ii); (C) normalized number of cells plotted as a function of pillar pitch.

Figure 3. (A) SEM images of a guided HL-1 cell on nanopillars with an interspace of 2 μm (scale bar 5 μm); (B) SEM images of a guided HL-1 cell
on nanopillars with an interspace of 10 μm (scale bar 8 μm).

For the analysis we first determined the absolute number of
cells on the samples and differentiated between cells on the
gold nanostructures and the silicon oxide areas (cells not being
fully on the pillars were counted as on the silicon oxide) and
accounted the underlying total area of both counts for the
normalization. The analyzed samples (n = 10) showed a high
cell vitality with nearly 100% living cells (calcein staining
marked in green in Figure 2A). To investigate the highest
guidance effect, the normalized number of cells was plotted as a
function of the pitch between adjacent pillars (Figure 2C). As
shown in the plot (Figure 2C), the normalized number of notguided cells was on average 10%, in contrast with the 90% of
the cells guided by the 3D gold nanostructures. We assume that
this is due to the fact that the effective adhesion area of the 3D
nanostructures is higher than the flat Si area and in principle
cardiomyocytes would rather anchor via focal adhesion proteins
and spread on the rough nanopillar surface than on the flat
surface. The nanopillars with a pitch from 3 to 7 μm were
shown to have the best guidance effect on the HL-1 cells: on
average 93−96% of cells were guided in this range of pitches in
contrast to only about 87% guided cells by a 2 μm pitch (Figure
2B,i) and an even lower degree of guided cells for pitches
between 8 and 10 μm (84−86%). Thus, we were able to guide

up to 96% of the cardiomyocytes in the presence of mushroomshaped structures with a 4 μm pitch (Figure 2B,ii). Similar
results were shown for LRM55 cells on silicon pillars36 where
70% of the cells have grown preferably on the 3D structures
than on smooth surface.
To investigate the performance of the nanopillars that
showed the lowest guidance effect, we performed on the pillars
with 2 and 10 μm additional scanning electron microscopy
(SEM). After the calcein stain, the cells were washed with
prewarmed PBS and fixed with 4% paraformaldehyde in PBS
for 10 min at room temperature. Dehydration was carried out
with ethanol in different concentrations ranging from 10% up
to 100% (v/v). Afterward, a critical point drying was performed
with CO2 as an intermediate medium for drying the cells. For
the SEM images, a thin layer of platinum was sputtered on the
sample, and a LEO 1550 (Carl Zeiss AG, Oberkochen,
Germany) scanning electron microscope was used for the
acquisition. For the acquisition a voltage of 20 kV was applied
using an “in lens” detector for the secondary electrons. The
images were then acquired in scanning electron mode. From
the SEM investigation, we noticed that the cardiomyocytes
tended to spread more and flattened in the presence of the
bigger pitch as shown in Figure 3B, still engulfing the 3D

dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Nano Letters


Figure 4. (A) FIB cross section of HL-1 on 2 μm pitch nanopillars (scale bar 4 μm, tilt 52°); (B) details of membrane not attached on the substrate
(scale bar 0.5 μm, tilt 52°); (C) FIB cross section of HL-1 on 10 μm pitch nanopillar (scale bar 5 μm, tilt 52°); (D) details of cell attaching the
nanopillar (scale bar 0.5 μm, tilt 52°).

Figure 5. (A) Spontaneous action potentials recorded by 3D electrodes in a time frame of 12 s; (B) single action potentials recording in a time frame
of 1.5 s.

1 cells grew on the 3D nanostructures (Figure 4C), while the
bottom membrane in addition spread when attaching the planar
gold surface below the pillars (Figure 4D).
For the voltage recording of extracellular signals, we
developed a 64 channel MEA amplifier system which consists
of a headstage and a main amplifier connected to a highresolution A/D converter (USB-6255, National Instruments,
Austin, Texas, USA) and to a controlling PC. A self-developed
LabView software (National Instruments, Austin, USA)
controls the recording of the data stream and allows to set
amplifier parameters such as gain and filter settings. The
headstage connects the MEA chip and amplifies the signal with
a gain of 10. The signal was further amplified with a gain of 100
in the main amplifier, resulting in a total nominal gain of 1000.
The amplifier system features a parallel readout of 64 channels
at a sampling rate of 10 kHz and can record voltages of less

nanostructures without being confined by them. On the other
hand, the cells have a more stretched configuration in the
presence of nanostructures with a 2 um pitch (Figure 3A): the
stretching is due to the cell phenotype where the cytoskeleton
rearrangement is driven mostly by myosin and actin filaments.
These phenomena were similarly discussed for groove
structures37−39 and for human fibroblasts.40
As an additional proof we accomplished a focused ion beam
(FIB) cross-section obtained with a Helios Nanolab Dual-beam
(FEI, Hillsboro, USA): the polishing and the milling of the
cross section have been performed using an ion voltage of 30
kV and current of 80 pA. We performed FIB cross sections for
the 2 and 10 μm pitches: in the case of the 2 μm pitch the cells
tended to grow completely on the top of the 3D nanostructures
(Figure 4A) without approaching the bottom part of the
substrate (Figure 4B). On the other hand, the 10 μm pitch HLD

dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Nano Letters


than 1 μV rms with a dynamic range of ±10 V (after
amplification). For cellular measurements we limited the
effective bandwidth with a high pass filter (AC coupling) and
a low pass filter (high frequency cutoff) from 1 Hz to 3 kHz.
The analysis of the data was performed with a script written in
MATLAB (Mathworks, Natick, USA) and ORIGIN (OriginLab, Northampton, USA).
The spontaneous activity of the HL-1 was recorded by the
3D nanostructured MEAs with a nominal electrode footprint of
8 μm diameter with mushroom nanopillars, and on the guiding
lines we fabricated nanopillars of a 4 μm pitch according to the
guidance results. The traces of spontaneous action potentials
are shown in Figure 5A, showing the voltage recordings of four
electrodes as a function of time. The frequency of the action
potentials amounted 0.62 ± 0.15 Hz for every trace of the
example. Due to the peculiar signal propagation of the
cardiomyocytes, it is possible to determine a signal propagation
speed of 28.6 mm/s. Considering an interval of 1−2 s (Figure
5B), one can calculate the delay between an action potential on
one electrode and another electrode serving as a reference in
To chemically stimulate the cells, norepinephrine was added
to cell media with a concentration of 1:1000. Norepinephrine
effects an increase of the contraction rate of the cardiomyocytes
(Figure 6), resulting in a frequency of about 0.89 ± 0.17 Hz in

have more than a 90% effective guidance effect on HL-1 cells.
Moreover, we were able to investigate the cell response to the
pillar interspace with focused ion beam cross sectioning and
scanning electron microscopy. These guidance results represent
an improvement compared to results obtained with other
techniques previously mentioned and in addition the 3D
nanostructure-based guidance represents a novel technique for
cell patterning. The mushroom-like structures are furthermore
suitable for extracellular recordings of action potentials and
combine effective cell guidance with electrophysiological
investigations for cardiomyocyte-like cells. To the knowledge
of the authors, this is one of the very few examples, potentially
the first, shown in the literature where a defined nanostructure
was used effectively and simultaneously for cell patterning and
extracellular measurements.


Corresponding Author

*E-mail: a.offenhaeusser@fz-juelich.de. Address: Leo Brandt
Strasse 1, 52428, Jülich, Germany. Tel. Office: +492461612330. Fax: +49246161-8733.

The authors declare no competing financial interest.

We would like to acknowledge Marco Banzet for the help in the
fabrication process. Unless otherwise noted, all the chemicals
were supplied by Sigma Aldrich GmbH, Seelze, Germany.


(1) Thomas, C. A., Jr.; Springer, P. A.; Loeb, G. E.; Berwald-Netter,
Y.; Okun, L. M. Exp. Cell Res. 1972, 74, 61−66.
(2) Gross, G. W.; Rieske, E.; Kreutzberg, G. W.; Meyer, A. Neurosci.
Lett. 1977, 6, 101−105.
(3) Pine, J. J. Neurosci. Methods 1980, 2, 19−31.
(4) Choi, D. S.; Fung, A. O.; Moon, H.; Villareal, G.; Chen, Y.; Ho,
D.; Presser, N.; Stupian, G.; Leung, M. J. Nanosci. Nanotechnol. 2009,
9, 6483−6486.
(5) Kim, J.-H.; Kang, G.; Nam, Y.; Choi, Y.-K. Nanotechnology 2010,
21, 085303.
(6) Wesche, M.; Hüske, M.; Yakushenko, A.; Brüggemann, D.;
Mayer, D.; Offenhäusser, A. Nanotechnology 2012, 23, 495303.
(7) Wang, K.; Fishman, H. A.; Dai, H.; Harris, J. S. Nano Lett. 2006,
6, 2043−2048.
(8) Yakushenko, A.; Gong, Z.; Maybeck, V.; Hofmann, B.; Gu, E.;
Dawson, M.; Offenhäusser, A.; Wolfrum, B. J. Biomed. Opt. 2013, 18,
(9) Verma, P.; Melosh, N. A. Appl. Phys. Lett. 2010, 97, 033704−
(10) Weis, R.; Fromherz, P. Phys. Rev. E 1997, 55, 877−889.
(11) Spira, M. E.; Hai, A. Nat. Nanotechnol. 2013, 8, 83−94.
(12) Brüggemann, D.; Wolfrum, B.; Maybeck, V.; Mourzina, Y.;
Jansen, M.; Offenhäusser, A. Nanotechnology 2011, 22, 265104.
(13) Keefer, E. W.; Botterman, B. R.; Romero, M. I.; Rossi, A. F.;
Gross, G. W. Nat. Nanotechnol. 2008, 3, 434−439.
(14) Gabay, T.; Ben-David, M.; Kalifa, I.; Sorkin, R.; Abrams, Z. R.;
Ben-Jacob, E.; Hanein, Y. Nanotechnology 2007, 18, 035201.
(15) Hai, A.; Shappir, J.; Spira, M. E. Nat. Methods 2010, 7, 200−202.
(16) Fendyur, A.; Spira, M. E. Front. Neuroeng. 2012, 5, 10.3389/
(17) Duan, X.; Gao, R.; Xie, P.; Cohen-Karni, T.; Qing, Q.; Choe, H.
S.; Tian, B.; Jiang, X.; Lieber, C. M. Nat. Nanotechnol. 2012, 7, 174−
(18) Hai, A.; Shappir, J.; Spira, M. E. J. Neurophysiol. 2010, 104, 559−

Figure 6. Action potentials recorded by 3D electrodes after chemical
stimulation with noradrenaline during a time frame of 12 s.

our experiment. Earlier works demonstrated the application of
nanostructured MEAs to be suitable for extracellular recordings
from HL-1 cells in the millivolt regime.6,12 On the other hand,
nanostructured MEA electrodes were successfully employed for
the recording of action potentials in the 10 mV range from
neuronal cell cultures.15 We show here the coupling of
cardiomyocytes on nanostructured electrodes. The recorded
signals from our gold nanopillars reached about 180 μV (peakto-peak) on some electrodes and were clearly distinguishable
from the background electrode noise. Xie et al.41 also measured
with their array of nanopillars (height 1.5 μm, diameter 150
nm) spontaneous activity from HL-1 cells in the range of about
100 μV (peak-to-peak) which is comparable with our results.
In conclusion, our 3D gold mushroom-shaped nanostructures were shown to be an appropriate tool for chip-based
simultaneous guidance and recording experiments. We were
able to determine that nanopillars with a pitch from 3 to 7 μm

dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Nano Letters


(19) Lu, Y.-B.; Franze, K.; Seifert, G.; Steinhäuser, C.; Kirchoff, F.;
Wolburg, H.; Guck, J.; Janmey, P.; Wei, E.-Q.; Käs, J.; Reichenbacj, A.
Proc. Natl. Acad. Sci. 2006, 103, 17759−17764.
(20) Sniadecki, N. J.; Desai, R. A.; Ruiz, S. A.; Chen, C. S. Ann.
Biomed. Eng. 2006, 34, 59−74.
(21) Andersson, A.-S.; Bäkhed, F.; von Euler, A.; Richter-Dahlfors,
A.; Sutherland, D.; Kasemo, B. Biomaterials 2003, 24, 3427−3436.
(22) Braeken, D.; Huys, R.; Jans, D.; Loo, J.; Rand, D. R.; Borghs, G.;
Callewaert, G.; Bartic, C. In World Congress Medical Physics and
Biomedical Engineering, Munich, Germany, Sept. 7−12, 2009; Dössel,
O., Schlegel, W. C., Eds.; Springer: Berlin, 2010; pp 212−215 and at
(23) Panaitov, G.; Thiery, S.; Hofmann, B.; Offenhäusser, A.
Microelectron. Eng. 2011, 88, 1840−1844.
(24) Hai, A.; Kamber, D.; Malkinson, G.; Erez, H.; Mazurski, N.;
Shappir, J.; Spira, M. E. J. Neur. Eng. 2009, 6, 066009.
(25) James, C. D.; Davis, R.; Meyer, M.; Turner, A.; Turner, S.;
Withers, G.; Kam, L.; Banker, G.; Craighead, H.; Issacson, M.; Turner,
J.; Shain, W. IEEE Trans. Biomed. Eng. 2000, 47, 17−21.
(26) Von Philipsborn, A. C.; Lang, S.; Bernhard, A.; Loeschinger, J.;
David, C.; Lehnert, D.; Bastmeyer, M.; Bonhoeffer, F. Nat. Protocols
2006, 1, 1322−1328.
(27) Cheng, J.; Zhu, G.; Wu, L.; Du, X.; Zang, H.; Wolfrum, B.; Jin,
Q.; Zhai, J.; Offenhäusser, A.; Xu, Y. J. Neurosci. Methods 2013, 213,
(28) Offenhäusser, A.; Böcker-Meffert, S.; Decker, T.; Helpenstein,
R.; Gasteier, P.; Groll, J.; Möller, M.; Reska, A.; Schäfer, S.; Schulte, P.;
Vogt-Eisele, A. Soft Matter 2007, 3, 290−298.
(29) Yu, T. W.; Bargmann, C. I. Nat. Neurosci. 2001, 4, 1169−1176.
(30) Au, T. H.; Cui, B.; Chu, Z. E.; Veres, T.; Radisic, M. Lab Chip
2009, 9, 564−575.
(31) Wang, L.; Liu, L.; Magome, N.; Agladze, K.; Chen, Y.
Biofabrication 2013, 5, 035013.
(32) Park, J.; Kim, H.-N.; Kim, D.-H.; Levchenko, A.; Suh, K.-Y.
IEEE Trans. NanoBiosci. 2012, 11, 28−36.
(33) Hofmann, B.; Kätelhön, E.; Schottdorf, M.; Offenhäusser, A.;
Wolfrum, B. Lab Chip 2011, 11, 1054−1058.
(34) Schnitker, J.; Afanasenkau, D.; Wolfrum, B.; Offenhäusser, A.
Phys. Status Solidi 2013, 210, 892−897.
(35) Claycomb, W. C.; Lanson, N. A.; Stallworth, B. S.; Egeland, D.
B.; Delcaprio, J. B.; Bahinski, A.; Izzo, N. J. Proc. Natl. Acad. Sci. 1998,
95, 2979−2984.
(36) Turner, A. M. P.; Dowell, N.; Turner, S. W. P.; Kam, L.;
Isaacson, M.; Turner, J. N.; Craighead, H. G.; Shain, W. J. Biomed.
Mater. Res. 2000, 51, 430−441.
(37) Kim, D.-H.; Lipke, E. A.; Kim, P.; Cheong, R.; Thompson, S.;
Delannoy, M.; Suh, K.-Y.; Tung, L.; Levchenko, A. Proc. Natl. Acad.
Sci. 2010, 107, 565−570.
(38) Nikkhah, M.; Edalat, F.; Manoucheri, S.; Khademhosseini, A.
Biomaterials 2012, 33, 5230−5246.
(39) Ross, A. M.; Jiang, Z.; Bastmeyer, M.; Lahann, J. Small 2012, 8,
(40) Kolind, K.; Dolatshahi-Pirouz, A.; Lovmand, J.; Pedersen, F. S.;
Foss, M.; Besenbacher, F. Biomaterials 2010, 31, 9182−9191.
(41) Xie, C.; Lin, Z.; Hanson, L.; Cui, Y.; Cui, B. Nat. Nanotechnol.
2012, 7, 185−190.


dx.doi.org/10.1021/nl402901y | Nano Lett. XXXX, XXX, XXX−XXX

Aperçu du document 1.pdf - page 1/6

Aperçu du document 1.pdf - page 2/6

Aperçu du document 1.pdf - page 3/6

Aperçu du document 1.pdf - page 4/6

Aperçu du document 1.pdf - page 5/6

Aperçu du document 1.pdf - page 6/6

Télécharger le fichier (PDF)

1.pdf (PDF, 1.5 Mo)

Sur le même sujet..

Ce fichier a été mis en ligne par un utilisateur du site. Identifiant unique du document: 00334744.
⚠️  Signaler un contenu illicite
Pour plus d'informations sur notre politique de lutte contre la diffusion illicite de contenus protégés par droit d'auteur, consultez notre page dédiée.