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Interfacing with the brain using organic electronics.
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Transcript of Interfacing with the brain using organic electronics.
Institut Mines‐Télécom
Interfacing with the brain using organic electronics
George MalliarasDepartment of Bioelectronics, Microelectronics Center of ProvenceEmail: [email protected] ; Twitter: @GeorgeMalliaras
Institut Mines‐Télécom
Our location
Department of Bioelectronics – www.bel.emse.fr2
Microelectronics Center of ProvenceInaugurated 2008
La Timone Hospital
AMU Medical School
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Outline
Introduction to neural interfacing
Why organics?
Conducting polymers yield new capabilities for neuroscience
• Recording single neurons without penetrating the brain
• Recording brain activity with high signal‐to‐noise ratio
• Stopping seizures (in vitro) with localized drug delivery
Ion transport in conducting polymers
Materials challenges ahead
Department of Bioelectronics – www.bel.emse.fr3
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Bioelectronics: Coupling biology and electronics
Department of Bioelectronics – www.bel.emse.fr4
Mostly soft
Complex signaling
Dynamic
Hard
Electrons/holes
Static
SensingDiagnosis
ActuationTherapy
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Importance of neural interfacing
100 billion neurons in the human brain, organized in networks
Their communication holds the key for understanding how the brain works
These networks can be rewired by diseases such as epilepsy, cancer, …
Stimulation of these networks is increasingly being used as therapy
Department of Bioelectronics – www.bel.emse.fr5
EEG ECoG sEEG
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Epilepsy
Affects 1‐2% of world population
Temporal lobe epilepsy (TLE) is most frequent form in adults
TLE is often drug resistant
Department of Bioelectronics – www.bel.emse.fr6
Key challenges:
Improve electrode performance
Make less invasive recordings
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Deep brain stimulation for Parkinson’s
Department of Bioelectronics – www.bel.emse.fr7
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Brain/machine interfaces
Department of Bioelectronics – www.bel.emse.fr8
L.R. Hochberg, D. Bacher, B. Jarosiewicz, N.Y. Masse, J.D. Simeral, J. Vogel, S. Haddadin, J. Liu, P. van der Smagt, and J.P. Donoghue, Nature 485, 372 (2012).
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From discovery to therapy
Department of Bioelectronics – www.bel.emse.fr9
Luigi Galvani(1737 – 1798)
Pacemaker circa 1957
Arne Larsson, first to receive implantable pacemaker in 1958. He received a total
of 26 pacemakers and died at 86.
NanostimLeadless pacemaker
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Implantable electronic medical devices
Department of Bioelectronics – www.bel.emse.fr10
Artificial limbs controlled by the brain(Penn Center for Brain Injury and Repair)
Cochlear implant(Cochlear)
Implantable defibrillator(Medtronic)
Approved devices:• Heart pacemakers – 600,000 per year• Cochlear implants (hearing) – 300,000 patients• Spinal cord stimulators (pain relief) – 15,000 per year• Deep brain stimulators (Parkinson’s)• Phrenic nerve stimulators (assisted breathing)• Sacral nerve stimulators (bladder control)• Vagus nerve stimulators (epilepsy)• Retinal implants (vision)
In development:• Functional electrical stimulation (standing and gait)• Brain Computer Interfaces (control of robotic limbs)• DBS (severe psychiatric conditions) • Vestibular prostheses (balance) • Vision prostheses (vision) • Cortical prostheses (epilepsy detection & suppression)
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Medical technologies raise ethical questions
Department of Bioelectronics – www.bel.emse.fr11
Young Frankenstein, 20th Century FOX (1974)
1771: Galvani’s experiments 1958: First implantable pacemaker Today: Implantable defibrillator
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Hype versus reality
Department of Bioelectronics – www.bel.emse.fr12
Dr. Octopus in Spiderman 2
Boy hearing for the first time
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Organic electronics
Department of Bioelectronics – www.bel.emse.fr13
Thin film transistors Photovoltaics
DuPont
Someya Lab
Light emitting diodes
Samsung
Astron FIAMM
Heliatek
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Typical organic semiconductors
Department of Bioelectronics – www.bel.emse.fr14
NN
CH3 CH3
O
NAl
3
TPD
Alq3
Pentacene
n n
S
O O
n
S n
PPPPPV
PEDOTP3HT
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Carbon as a semiconductor
Department of Bioelectronics – www.bel.emse.fr15
R. Hoffman, C. Janiak, C. Kollmar, Macromolecules 24, 13, 3725‐3746, (1991).
EG ħ2p22maN
CH2=CH2
Hybridization: sp2 and pZ
Particle in a box:
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PEDOT doped with PSS
Department of Bioelectronics – www.bel.emse.fr16
SO3H SO3H SO3H SO3H SO3- SO3H SO3H SO3H
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
+ *
p‐type doped material
Holes on PEDOTSulfonate ions on PSS
Holes in the form of polaronsPolyanion immobilizes dopants
σ = 1000 S/cm
Electrically neutral
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Conducting polymers match properties of tissue
Department of Bioelectronics – www.bel.emse.fr17
Slide courtesy of Dave Martin (U. Delaware)
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Conducting polymers show mixed conductivity
Department of Bioelectronics – www.bel.emse.fr18
J. Rivnay, R.M. Owens, and G.G. Malliaras, Chem. Mater. 26, 679 (2014).
Mixed conductivity leads to novel/state‐of‐the‐art devices
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Conducting polymer microelectrodesrecord single neurons from brain surface
Department of Bioelectronics – www.bel.emse.fr19
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Levels of neural interfacing
Department of Bioelectronics – www.bel.emse.fr20
schalklab.org
Ultimate resolution
EEG: Network level (~ 1 cm)
ECoG: Intermediate
sEEG: Single neuron (~ 10 µm)
It was not considered possible to obtain single neuron recordingswithout penetrating the brain
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State‐of‐the‐art ECoG circa 2010
Department of Bioelectronics – www.bel.emse.fr21
Rogers group (UIUC)
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Conducting polymers improve neural interfaces
Department of Bioelectronics – www.bel.emse.fr22
Work of Martin, Wallace, Inganäs, …
Electrochemical growth on pre‐patterned metal
electrodes
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Conducting polymers lower interfacial impedance
Department of Bioelectronics – www.bel.emse.fr23
Different “nature” of capacitance across the electrode/electrolyte interface
+++++
-----
MetalAu
PEDOT:PSS+
++
+
++
++
+
+-
+
-
-
--
---
--
Polymer
SO3H SO3H SO3H SO3H SO3- SO3H SO3H SO3H
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
+ *
Similar roughness
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Ultra‐conformable PEDOT:PSS microelectrodes
Department of Bioelectronics – www.bel.emse.fr24
D. Khodagholy, T. Doublet, M. Gurfinkel, P. Quilichini, E. Ismailova, P. Leleux, T. Herve, S. Sanaur, C. Bernard, and G.G. Malliaras, Adv. Mater. 36, H268 (2011).
Parylene C – 4 μm thickPEDOT:PSS
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Ultra‐conformable ECoG arrays
Department of Bioelectronics – www.bel.emse.fr25
w/ Christophe Bernard (INSERM)
50 μm
d=2.2mm
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PEDOT:PSS electrodes outperform Au electrodes
Department of Bioelectronics – www.bel.emse.fr26
w/ Christophe Bernard (INSERM)D. Khodagholy, T. Doublet, M. Gurfinkel, P. Quilichini, E. Ismailova, P. Leleux, T. Herve, S. Sanaur, C. Bernard, and G.G. Malliaras, Adv. Mater. 36, H268 (2011).
Auelectrodes
PEDOT:PSSelectrodes
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Detection of single neurons from brain surface
Department of Bioelectronics – www.bel.emse.fr27
w/ Dion Khodagholy, György Buzsáki (NYU)D. Khodagholy, J.N. Gelinas, T. Thesen, W. Doyle, O. Devinsky, G.G. Malliaras and G. Buzsáki, Natrure Neurosci. 18, 310 (2015)
10 ms by 50 mV
Electrocorticography in rats
256 electrodes, 10 x 10 μm2 with 30 μm inter‐electrode spacing
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Translation to the clinic
Department of Bioelectronics – www.bel.emse.fr28
w/ Dion Khodagholy, György Buzsáki (NYU)D. Khodagholy, J.N. Gelinas, T. Thesen, W. Doyle, O. Devinsky, G.G. Malliaras and G. Buzsáki, Natrure Neurosci. 18, 310 (2015)
500 ms by 500 mV
20 ms by 40 mV
Acute recordings in human patients
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Organic electrochemical transistors record brain activity with record‐high SNR
Department of Bioelectronics – www.bel.emse.fr29
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Field‐effect transistors for neural recordings
Department of Bioelectronics – www.bel.emse.fr30
Field‐effect transistor (FET)C’max = 5 μF/cm2
M. Voelker and P. Fromherz, Small 1, 206 (2005).
SiO2
+++++ Vg
IdSi++++
- - - - - - - - -
Fromherz group, MPI
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The organic electrochemical transistor (OECT)
Department of Bioelectronics – www.bel.emse.fr31
No insulator between channel and electrolyte
First OECT: H.S. White, G.P. Kittlesen, and M.S. Wrighton, J. Am. Chem. Soc. 106, 5375 (1984).
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Volumetric response of capacitance in PEDOT:PSS
Department of Bioelectronics – www.bel.emse.fr32
For d=130 nm:C’ = 500 μF/cm2
100× larger than double layer capacitance
C* = 39 F/cm3
J. Rivnay, P. Leleux, M. Ferro, M. Sessolo, A. Williamson, D.A. Koutsouras, D. Khodagholy, M. Ramuz, X. Strakosas, R.M. Owens, C. Benar, J.‐M. Badier, C. Bernard, and G.G. Malliaras, SCIENCE Advances 1, e1400251 (2015).
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Device model
Department of Bioelectronics – www.bel.emse.fr33
dx
V(x)
Vg
cd W dx
Rs
......
Q(x)
D.A. Bernards and G.G. Malliaras, Adv. Funct. Mater. 17, 3538 (2008)
Ionic circuit(electrochemistry)
Electronic circuit(solid state physics)
-- -- -
++
-
+
- -
-
+
+Gate Electrode
+
-
++
++
+ + +
+
+
SO3H SO3H SO3H SO3H SO3- SO3H SO3H SO3H
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
S
O O
+ *
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Characteristics of OECTs
Department of Bioelectronics – www.bel.emse.fr34
J. Rivnay, P. Leleux, M. Sessolo, D. Khodagholy, T. Hervé, M. Fiocchi, G. G. Malliaras, Adv. Mater. 25, 7010 (2013).
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High transconductance OECTs
Department of Bioelectronics – www.bel.emse.fr35
D. Khodagholy, J. Rivnay, M. Sessolo, M. Gurfinkel, P. Leleux, L.H. Jimison, E. Stavrinidou, T. Herve, S. Sanaur, R.M. Owens, and G.G. Malliaras, Nature Comm. 4, 2133 (2013).
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In vivo recordings using transistors
Department of Bioelectronics – www.bel.emse.fr36
w/ Christophe Bernard (INSERM)
Transistor
SNR = 52.7 dB
SNR = 30.2 dB
1 μA
10 mV
1 s
Electrode
D. Khodagholy, T. Doublet, P. Quilichini, M. Gurfinkel, P. Leleux, A. Ghestem, E. Ismailova, T. Herve, S. Sanaur, C. Bernard, and G.G. Malliaras , Nature Comm. 4, 1575 (2013).
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Transistors enable less invasive recordings
Department of Bioelectronics – www.bel.emse.fr37
w/ Christophe Bernard (INSERM) D. Khodagholy, T. Doublet, P. Quilichini, M. Gurfinkel, P. Leleux, A. Ghestem, E. Ismailova, T. Herve, S. Sanaur, C. Bernard, and G.G. Malliaras , Nature Comm. 4, 1575 (2013).
Transistor
Surfaceelectrode
Depthelectrode
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Model for OECT operation
Department of Bioelectronics – www.bel.emse.fr38
SO3-
SO3-
SO3- SO3
-
SO3-
++
++
++SO3
-
M+
ID=W∙d∙e∙μ∙p(x)∙[dV(x)/dx]
IDp(x)=SO3
‐ – M+(x)
M+(x)=(C*/e)∙[VG – V(x)]
Integrating Id over the length of the channel:
ID=(W∙d/L)∙μ∙C*∙[VT – VG + VD/2]∙VD IDSAT=[W /(2∙L)] ∙d ∙μ∙C*∙[VT – VG]2
VT= e∙SO3‐/C*
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Scaling with geometry
Department of Bioelectronics – www.bel.emse.fr39
b
10-5 10-4 10-310-5
10-4
10-3
(s)
RS C (s)
∙ ∙ ∙ ∗ ∙J. Rivnay, P. Leleux, M. Ferro, M. Sessolo, A. Williamson, D.A. Koutsouras, D. Khodagholy, M. Ramuz, X. Strakosas, R.M. Owens, C. Benar, J.‐M. Badier, C. Bernard, and G.G. Malliaras, SCIENCE Advances1, e1400251 (2015).
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High transconductance means high SNR
Department of Bioelectronics – www.bel.emse.fr40
w/ Christian Benar, Jean‐Michel Badier Bernard (INSERM)
J. Rivnay, P. Leleux, M. Ferro, M. Sessolo, A. Williamson, D.A. Koutsouras, D. Khodagholy, M. Ramuz, X. Strakosas, R.M. Owens, C. Benar, J.‐M. Badier, C. Bernard, and G.G. Malliaras, SCIENCE Advances 1, e1400251 (2015).
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Organic electronic ion pumpscontrol epileptiform activity
Department of Bioelectronics – www.bel.emse.fr41
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The organic electronic ion pump
Department of Bioelectronics – www.bel.emse.fr42
Work at Linkoping University and Karolinska InstituteD. T. Simon, S. Kurup, K. C. Larsson, R. Hori, K. Tybrandt,
M. Goiny, E. H. Jager, M. Berggren, B. Canlon, and A. Richter‐Dahlfors, Nature Materials 8, 742 (2009).
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Ion pump operation
Department of Bioelectronics – www.bel.emse.fr43
-- ---+
++
- -
+ ++++
++
- - - - - -- -
--
--- +
+
+
++
+ +
++
+
PEDOT:PSS PEDOT:PSSPSS
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Ion pump for local delivery in neural networks
Department of Bioelectronics – www.bel.emse.fr44
w/ Christophe Bernard (INSERM), Magnus Berggren (Linköping)
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Local delivery of GABA suppress seizure activity
Department of Bioelectronics – www.bel.emse.fr45
w/ Christophe Bernard (INSERM), Magnus Berggren (Linköping)
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Local delivery of GABA suppress seizure activity
Department of Bioelectronics – www.bel.emse.fr46
w/ Christophe Bernard (INSERM), Magnus Berggren (Linköping)
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Scaling with geometry
Department of Bioelectronics – www.bel.emse.fr47
b
10-5 10-4 10-310-5
10-4
10-3
(s)
RS C (s)
∙ ∙ ∙ ∗ ∙J. Rivnay, P. Leleux, M. Ferro, M. Sessolo, A. Williamson, D.A. Koutsouras, D. Khodagholy, M. Ramuz, X. Strakosas, R.M. Owens, C. Benar, J.‐M. Badier, C. Bernard, and G.G. Malliaras, SCIENCE Advances1, e1400251 (2015).
Institut Mines‐Télécom Department of Bioelectronics – www.bel.emse.fr48
1 10 100 10000.01
0.1
1
10
e (cm
2 /Vs)
C* (F/cm3)
+EG,GOPSPEDOT:PSS
+EG,GOPSP3HT‐SO3‐
Recent New High‐performer(Iain McCulloch, Imperial)
0% EG
50% EG
5‐10% EG
μC* as the materials figure of merit
S
SOO
O
* n
-(C4H9)4N+
P3HT‐SO3‐
(+EG +GOPS)
μC* = 7.2 F/cmVsμ = 0.05 cm2/VsC* = 144 F/cm3
w/ M. Thelakkat, U. Bayreuth
S. Inal, J. Rivnay, P. Leleux, M. Ferro, M. Ramuz, J.C. Brendel, M. Schmidt, M. Thelakkat, and G.G. Malliaras, Adv. Mater. 26, 7450 (2014).
PEDOT:PSS(+EG, +GOPS)
μC* = 128 F/cmVsμ = 3.3 cm2/VsC* = 39 F/cm3
Such maps provide a way to compare materials as potential
candidates in OECTs
Institut Mines‐Télécom Department of Bioelectronics – www.bel.emse.fr49
PEDOT:PSS as a champion material
Phase separated morphology
Hole transport in PEDOT‐rich domains, ion transport in PSS matrix
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“Moving front” measurements
Department of Bioelectronics – www.bel.emse.fr50
K. Aoki, T. Aramoto and Y. Hoshino, Journal of Electroanalytical Chemistry 340, 127 (1992).T. Johansson, N. K. Persson and O. Inganas, Journal of the Electrochemical Society 151, E119 (2004).
X. Wang and E. Smela, The Journal of Physical Chemistry C 113, 369 (2008).
holesions 2D geometry makes
analysis difficult
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A simple way to measure ion transport
Department of Bioelectronics – www.bel.emse.fr51
Glass
Electrolyte PEDOT:PSS Au
Vappl
Dedoped Doped
Barrier
+‐+
‐
++
++ SO3
-
SO3-
SO3-
SO3-
SO3-
SO3-
SO3-
SO3-
SO3-
SO3-
++
++
++
E. Stavrinidou, P. Leleux, H. Rajaona, D. Khodagholy, J. Rivnay, M. Lindau, S. Sanaur, and G.G. Malliaras, Adv. Mater. 25, 4488 (2013).
RI RC
ℓ ∙ ∙
∙ 2 ∙ ∙2
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Ions are highly mobile in PEDOT:PSS
Department of Bioelectronics – www.bel.emse.fr52
E. Stavrinidou, P. Leleux, H. Rajaona, D. Khodagholy, J. Rivnay, M. Lindau, S. Sanaur, and G.G. Malliaras, Adv. Mater. 25, 4488 (2013).
K+ mobility in film
( )
K+ density in film
(cm‐3)
PEDOT:PSS 1.4 ∙ 10 5.9 ∙ 10
PEDOT:PSS :GOPS 1.9 ∙ 10 3.2 ∙ 10
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Linking ion transport and electrode impedance
Department of Bioelectronics – www.bel.emse.fr53
E. Stavrinidou, M. Sessolo, B. Winther‐Jensen, S. Sanaur, and G.G. Malliaras, AIP Advances 4, 017127 (2014).
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Open questions
We should leverage our understandingof electronic processes in organics
How do we envision ion injection• Field‐dependence?• Hydrophilicity, hydration?• Connection to mechanical properties?• Dependence on ion size?
What is the optimal material• Balance between crystalline and amorphous domains?• Separate paths of ionic/electronic transport – copolymers?
Characterization in aqueous media
Department of Bioelectronics – www.bel.emse.fr54
metal polymer
+‐+
electrolyte
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Conclusions
Organic bioelectronics represents an emerging research direction.
Conducting polymers are leading to new capabilities for neuroscience:• Non‐invasive, high SNR recordings of brain activity in animal models
and in the clinic• Localized drug delivery that can stop seizure in in vitromodel
Mixed conductivity of organics a key advantage.
We need to leverage advances in understanding electronic structure & transport to describe mixed conductivity and design better materials.
Department of Bioelectronics – www.bel.emse.fr55
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Acknowledgements Neuroengineering team at BEL
Jonathan Rivnay, Sahika Inal, Mary Donahue, Marc Ferro, Dimitris Koutsouras, Thomas Lonjaret, Ilke Uguz, Eloise Bihar, Marcel Brändlein, Shahab Rezaei Mazinani, JolienPas, Esma IsmailovaColleagues @ BEL: Xenofon Strakosas, Roisin Owens
Institute of Systems NeuroscienceAnimal research: Adam Williamson, Attila Kaszas, Christophe Bernard Clinical: Jean‐Michel Badier, Christian Benar
University of Linköping (Sweden)Amanda Jonsson, Loig Kergoat, Daniel Simon, Magnus Berggren
Microvitae TechnologiesPierre Leleux, Thierry Hervé
Other Collaborators Dion Khodagholy, György Buzsáki (NYU), Michele Sessolo (Valencia), Seiichi Takamatsu (AIST), Marc Ramuz (EMSE).
Department of Bioelectronics – www.bel.emse.fr56
For more information:
Department of Bioelectronics (BEL)