Interfacing with the brain using organic electronics.
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![Institut Mines‐Télécom
Model for OECT operation
Department of Bioelectronics – www.bel.emse.fr38
SO3
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SO3
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SO3
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SO3
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+SO3
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M+
ID=W∙d∙e∙μ∙p(x)∙[dV(x)/dx]
ID
p(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 ID
SAT=[W /(2∙L)] ∙d ∙μ∙C*∙[VT – VG]2
VT= e∙SO3
‐/C*](https://image.slidesharecdn.com/malliarasplenary-151026200549-lva1-app6891/75/interfacing-with-the-brain-using-organic-electronics-38-2048.jpg?cb=1667981511)
Interfacing with the brain using organic electronics.
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Plenary lecture of the XIV SBPMat Meeting, given by Prof. George Malliaras (École Nationale Supérieure des Mines de Saint-Étienne, France) on September 30, 2015, in Rio de Janeiro (Brazil).
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Interfacing with the brain using organic electronics.
- 3. Institut Mines‐Télécom 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
- 5. Institut Mines‐Télécom 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
- 6. Institut Mines‐Télécom 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
- 9. Institut Mines‐Télécom 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. Nanostim Leadless pacemaker
- 10. Institut Mines‐Télécom 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)
- 11. Institut Mines‐Télécom 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
- 14. Institut Mines‐Télécom Typical organic semiconductors Department of Bioelectronics – www.bel.emse.fr14 NN CH3 CH3 O N Al 3 TPD Alq3 Pentacene nn S O O n S n PPP PPV PEDOT P3HT
- 15. Institut Mines‐Télécom Carbon as a semiconductor Department of Bioelectronics – www.bel.emse.fr15 R. Hoffman, C. Janiak, C. Kollmar, Macromolecules 24, 13, 3725‐3746, (1991). EG ħ2p2 2maN CH2=CH2 Hybridization: sp2 and pZ Particle in a box:
- 16. Institut Mines‐Télécom PEDOT doped with PSS Department of Bioelectronics – www.bel.emse.fr16 SO3 H SO3 H SO3 H SO3 H SO3 - SO3 H SO3 H SO3 H 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 PEDOT Sulfonate ions on PSS Holes in the form of polarons Polyanion immobilizes dopants σ = 1000 S/cm Electrically neutral
- 23. Institut Mines‐Télécom Conducting polymers lower interfacial impedance Department of Bioelectronics – www.bel.emse.fr23 Different “nature” of capacitance across the electrode/electrolyte interface + + + + + - - - - - Metal Au PEDOT:PSS + + + + + + + + + + - + - - - - - - - - - Polymer SO3H SO3 H 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
- 25. Institut Mines‐Télécom Ultra‐conformable ECoG arrays Department of Bioelectronics – www.bel.emse.fr25 w/ Christophe Bernard (INSERM) 50 μm d=2.2mm
- 27. Institut Mines‐Télécom 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
- 28. Institut Mines‐Télécom 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
- 30. Institut Mines‐Télécom 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 Id Si ++++ - - - - - - - - - Fromherz group, MPI
- 32. Institut Mines‐Télécom 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).
- 33. Institut Mines‐Télécom 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 SO3 H SO3 - SO3H SO3H SO3 H S O O S O O S O O S O O S O O S O O S O O S O O + *
- 38. Institut Mines‐Télécom 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] ID p(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 ID SAT=[W /(2∙L)] ∙d ∙μ∙C*∙[VT – VG]2 VT= e∙SO3 ‐/C*
- 39. Institut Mines‐Télécom Scaling with geometry Department of Bioelectronics – www.bel.emse.fr39 b 10 -5 10 -4 10 -3 10 -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).
- 43. Institut Mines‐Télécom Ion pump operation Department of Bioelectronics – www.bel.emse.fr43 -- -- - + + + - - + ++++ ++ - - - - - - - - - - --- + + + + + + + + + + PEDOT:PSS PEDOT:PSSPSS
- 47. Institut Mines‐Télécom Scaling with geometry Department of Bioelectronics – www.bel.emse.fr47 b 10 -5 10 -4 10 -3 10 -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).
- 48. Institut Mines‐Télécom Department of Bioelectronics – www.bel.emse.fr48 1 10 100 1000 0.01 0.1 1 10 e (cm 2 /Vs) C* (F/cm 3 ) +EG,GOPS PEDOT:PSS +EG,GOPS P3HT‐SO 3‐ Recent New High‐performer (Iain McCulloch, Imperial) 0% EG 50% EG 5‐10% EG μC* as the materials figure of merit S SO O O * n - (C4H9)4N+ P3HT‐SO3 ‐ (+EG +GOPS) μC* = 7.2 F/cmVs μ = 0.05 cm2/Vs C* = 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/cmVs μ = 3.3 cm2/Vs C* = 39 F/cm3 Such maps provide a way to compare materials as potential candidates in OECTs
- 49. 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
- 50. Institut Mines‐Télécom “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). holes ions 2D geometry makes analysis difficult
- 51. Institut Mines‐Télécom 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
- 52. Institut Mines‐Télécom 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
- 54. Institut Mines‐Télécom Open questions We should leverage our understanding of 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
- 55. Institut Mines‐Télécom 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 vitro model 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
- 56. Institut Mines‐Télécom 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, Jolien Pas, Esma Ismailova Colleagues @ BEL: Xenofon Strakosas, Roisin Owens Institute of Systems Neuroscience Animal 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 Technologies Pierre 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)