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Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site
Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
Department of Bioelectronics, Ecole Nationale Supérieure des Mines, CMP-EMSE, MOC, Gardanne, France .
Department of Bioelectronics, Ecole Nationale Supérieure des Mines, CMP-EMSE, MOC, Gardanne, France .
Aix Marseille Université, INS, Marseille, France; Inserm, UMR_S 1106, Marseille, France.
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2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 34, 9440-9445 p.Article in journal (Refereed) Published
Abstract [en]

Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules at the same site for the most efficient feedback regulation. Here, we address this challenge with an organic electronic multifunctional device that is capable of chemical stimulation and electrical sensing at the same site, at the single-cell scale. Conducting polymer electrodes recorded epileptiform discharges induced in mouse hippocampal preparation. The inhibitory neurotransmitter, γ-aminobutyric acid (GABA), was then actively delivered through the recording electrodes via organic electronic ion pump technology. GABA delivery stopped epileptiform activity, recorded simultaneously and colocally. This multifunctional “neural pixel” creates a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents.

Place, publisher, year, edition, pages
National Academy of Sciences , 2016. Vol. 113, no 34, 9440-9445 p.
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
URN: urn:nbn:se:liu:diva-130851DOI: 10.1073/pnas.1604231113ISI: 000381860800035PubMedID: 27506784OAI: oai:DiVA.org:liu-130851DiVA: diva2:955872
Note

Funding agencies:We thank Gaelle Rondeau and the staff of the clean room in Centre Microelectronique de Provence (CMP) for technical support during fabrication. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 602102 (EPITARGET) and Initiative of Excellence Aix-Marseilles project MIDOE (A_M-AAP-ID-13-24-130531-16.31-BERNARD-HLS). Funding was also provided by the Swedish Innovation Office (2010-00507), the Swedish Research Council (621-2011-3517), and the Knut and Alice Wallenberg Foundation (KAW Scholar, 2012.0302). The authors also thank the National Science Foundation Grant DMR-1105253 for partial support of this work, the French National Research Agency (ANR) through the project PolyProbe (ANR-13-BSV5-0019-01), Fondation pour la Recherche Medicale under Grant Agreements DBS20131128446 and ARF20150934124, Fondation de l'Avenir, the Onnesjo Foundation, the Region Provence-Alpes-Cote d'Azur, and Microvitae Technologies. J.R. and L.K. acknowledge support from Marie Curie Fellowships. The fabrication of the device was performed, in part, at CMP.

Available from: 2016-08-26 Created: 2016-08-26 Last updated: 2017-11-21Bibliographically approved
In thesis
1. Organic electronics for precise delivery of neurotransmitters
Open this publication in new window or tab >>Organic electronics for precise delivery of neurotransmitters
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organic electronic materials, that is, carbon-based compounds that conduct electricity, have emerged as candidates for improving the interface between conventional electronics and biological systems. The softness of these materials matches the elasticity of biological tissue better than conventional electronic conductors, allowing better contact to tissue, and the mixed ionic-electronic conductivity can improve the signal transduction between electronic devices and electrically excitable cells. This improved communication between electronics and tissue can significantly enhance, for example, electrical stimulation for therapy and electrical recording for diagnostics.

The ionic conductivity of organic electronic materials makes it possible to achieve ion-specific ionic currents, where the current consists of migration of specific ions. These ions can be charged signalling substances, such as neurotransmitters, that can selectively activate or inhibit cells that contain receptors for these substances. This thesis describes the development of chemical delivery devices, where delivery is based on such ion-specific currents through ionically and electronically conducting polymers. Delivery is controlled by electrical signals, and allows release of controlled amounts of neurotransmitters, or other charged compounds, to micrometer-sized regions.

The aims of the thesis have been to improve spatial control and temporal resolution of chemical delivery, with the ultimate goal of selective interaction with individual cells, and to enable future therapies for disorders of the nervous system. Within the thesis, we show that delivery can alleviate pain through local delivery to specific regions of the spinal cord in an animal model of neuropathic pain, and that epilepsy-related signalling can be suppressed in vitro. We also integrate the delivery device with electrodes for sensing, to allow simultaneous electrical recording and delivery at the same position. Finally, we improve the delay from electrical signal to chemical delivery, approaching the time domain of synaptic signaling, and construct devices with several individually controlled release sites.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 108 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1817
National Category
Textile, Rubber and Polymeric Materials Condensed Matter Physics Biomedical Laboratory Science/Technology Materials Chemistry Neurosciences
Identifiers
urn:nbn:se:liu:diva-133164 (URN)10.3384/diss.diva-133164 (DOI)978-91-7685-616-1 (ISBN)
Public defence
2017-01-11, Kåkenhus sal K3 (Önnesjösalen), Linköpings Universitet, Norrköping, 10:00 (English)
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Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2017-02-03Bibliographically approved

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Jonsson, AmandaKergoat, LoigBerggren, MagnusSimon, Daniel T

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