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Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function

Nature Materials volume 8, pages 742–746 (2009)Cite this article

Abstract

Significant advances have been made in the understanding of the pathophysiology, molecular targets and therapies for the treatment of a variety of nervous-system disorders. Particular therapies involve electrical sensing and stimulation of neural activity1,2,3,4, and significant effort has therefore been devoted to the refinement of neural electrodes5,6,7,8. However, direct electrical interfacing suffers from some inherent problems, such as the inability to discriminate amongst cell types. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmitters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmitters, the device mimics the nerve synapse. Using the peripheral auditory system, we show that out of a diverse population of cells, the device can selectively stimulate nerve cells responding to a specific neurotransmitter. This is achieved by precise electronic control of electrophoretic migration through a polymer film. This mechanism provides several sought-after features for regulation of cell signalling: exact dosage determination through electrochemical relationships, minimally disruptive delivery due to lack of fluid flow, and on–off switching. This technology has great potential as a therapeutic platform and could help accelerate the development of therapeutic strategies for nervous-system disorders.

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Figure 1: Planar and encapsulated geometries of the delivery device.
Figure 2: Transport of neurotransmitters in the planar delivery device.
Figure 3: Glu-induced Ca2+ responses in astrocytes.
Figure 4: In vivo application of the ion pump.

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Acknowledgements

We wish to thank S. Plantman for providing primary astrocyte cultures, J. Kehr for access to the HPLC equipment, A. Viberg for technical assistance and D. Nilsson, P. Kjäll and T. Nakagawa for valuable discussion. This project has been carried out within the Strategic Research Center for Organic Bioelectronics (OBOE, www.oboe.nu) funded by the Swedish Foundation for Strategic Research (SSF). The Organic Electronics Group at Linköping University in Norrköping is a member of the COE@COIN project, also funded by the SSF. B.C. is supported by the Swedish Research Council, Funds of Karolinska Institutet and Tysta Skolan. The agencies that have supported this study were not involved in the design, interpretation, analysis or review of the data.

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Author notes

  1. Ryusuke Hori

    Present address: Present address: Department of Otolaryngology, Head & Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan,

Authors and Affiliations

  1. Department of Science and Technology (ITN), Linköping University, S-601 74 Norrköping, Sweden

    Daniel T. Simon, Klas Tybrandt, Edwin W. H. Jager & Magnus Berggren

  2. Strategic Research Center for Organic Bioelectronics (OBOE), Linköping and Stockholm, Sweden

    Daniel T. Simon, Sindhulakshmi Kurup, Karin C. Larsson, Klas Tybrandt, Edwin W. H. Jager, Magnus Berggren & Agneta Richter-Dahlfors

  3. Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden

    Sindhulakshmi Kurup, Karin C. Larsson & Agneta Richter-Dahlfors

  4. Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden

    Ryusuke Hori, Michel Goiny & Barbara Canlon

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Contributions

D.T.S. was responsible for the design, characterization and operation of the encapsulated device, and primary preparation of the manuscript. S.K. characterized the planar devices and K.C.L. carried out in vitro cell experiments and assisted with operation of the devices in vivo. R.H. and B.C. carried out the surgical procedure and subsequent audiological and physiological analysis. K.T. manufactured the planar devices, M.G. carried out HPLC analysis and both K.T. and E.W.H.J. aided in the design of the encapsulated device. M.B., B.C. and A.R.-D. are the senior authors of the paper. Each was responsible for supervision in their respective departments, as well as project planning and preparation of the manuscript.

Corresponding authors

Correspondence to Ryusuke Hori or Agneta Richter-Dahlfors.

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Simon, D., Kurup, S., Larsson, K. et al. Organic electronics for precise delivery of neurotransmitters to modulate mammalian sensory function. Nature Mater 8, 742–746 (2009). https://doi.org/10.1038/nmat2494

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