Controlling Epileptiform Activity with Organic Electronic Ion Pumps

Williamson, Adam; Rivnay, Jonathan; Kergoat, Loïg; Jönsson, Anna K.; Inal, Sahika; Uguz, Ilke; Ferro, Marc; Ivanov, Anton; Sjöström, Theresia Arbring; Simon, Daniel T.; Berggren, Magnus; Malliaras, George G.; Bernard, Christophe

doi:10.1002/adma.201500482

Cited by 155 publications

(154 citation statements)

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“…22 and Fig. S5), and local control of hippocampal networks with a similar device geometry (21). Taken together, these results demonstrate that the neural pixel system can effectively control the activity of a given network via OEIP delivery, while simultaneously allowing monitoring via the integrated electrodes of both hyperactivity and real-time biological response to OEIP operation.…”

Section: In Vitro Validation With Complete Hippocampus Preparations: mentioning

confidence: 52%

“…This is a necessary advancement to achieve highly localized feedback-regulated therapies with future devices. We have previously shown that we could deliver GABA with an OEIP to stop epileptiform activity in a tissue slice (21). In those experiments, the recording electrode was a tungsten electrode positioned in the tissue slice in the vicinity of an OEIP outlet.…”

Section: Discussionmentioning

confidence: 99%

“…The OEIP uses conducting polymer electrodes to electrophoretically "pump" neurotransmitters through a permselective membrane, enabling high spatiotemporal delivery resolution, without necessitating liquid flow. OEIPs have been used in vitro to trigger cell signaling (18,20) and to control epileptiform activity in vitro (21), as well as in vivo to effect sensory function (19) and as a therapy for pain in awake animals (22). OEIPs have also been demonstrated in a biosensor-regulated system-on a macroscopic scale-to mimic the chemical-to-electrical-to-chemical signal transduction of neurons (23).…”

Section: Significancementioning

confidence: 99%

“…per outlet; this corresponds to a local concentration change of 25 μM at a distance of 400 μm from a single pump outlet (18,21) after 60 s, and is within the known range for GABA to suppress hyperactivity (26) [injection of 250 μM of GABA in the ACSF-filled bath directly on top of the tissue stopped the hyperactivity almost instantaneously (Fig. S4)].…”

Section: In Vitro Validation With Complete Hippocampus Preparations: mentioning

confidence: 99%

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Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site

Jönsson

Inal

Uguz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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117

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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.

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.

show abstract

Section: In Vitro Validation With Complete Hippocampus Preparations: mentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Section: In Vitro Validation With Complete Hippocampus Preparations: mentioning

confidence: 99%

See 2 more Smart Citations

Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the same site

Jönsson

Inal

Uguz

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

117

View full text Add to dashboard Cite

show abstract

“…Devices known as organic electronic ion pumps respond to an applied voltage by forcing drugs -small charged particles -out of a reservoir. Working with the group at Linköping University and the French National Institute of Health and Medical Research in Marseilles, Malliaras's team is coupling his epilepsy sensor to an ion pump that responds to seizures by releasing epilepsy drugs into the correct part of the brain 8 . Berggren and the Linköping team have used a similar technique to develop a 'pacemaker for pain' that delivers analgesics directly to the spinal cord 9 .…”

Section: "I Haven't Found Any Clinical Folks Who Say 'That's Pie In mentioning

confidence: 99%