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A transparent organic transistor structure for bidirectional stimulation and recording of primary neurons

Nature Materials volume 12, pages 672–680 (2013)Cite this article

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Abstract

Real-time stimulation and recording of neural cell bioelectrical activity could provide an unprecedented insight in understanding the functions of the nervous system, and it is crucial for developing advanced in vitro drug screening approaches. Among organic materials, suitable candidates for cell interfacing can be found that combine long-term biocompatibility and mechanical flexibility. Here, we report on transparent organic cell stimulating and sensing transistors (O-CSTs), which provide bidirectional stimulation and recording of primary neurons. We demonstrate that the device enables depolarization and hyperpolarization of the primary neuron membrane potential. The transparency of the device also allows the optical imaging of the modulation of the neuron bioelectrical activity. The maximal amplitude-to-noise ratio of the extracellular recording achieved by the O-CST device exceeds that of a microelectrode array system on the same neuronal preparation by a factor of 16. Our organic cell stimulating and sensing device paves the way to a new generation of devices for stimulation, manipulation and recording of cell bioelectrical activity in vitro and in vivo.

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Figure 1: Physiology of neurons on a P13 thin film and electrical characteristics of the O-CST device before and after exposure to the physiological environment.
Figure 2: Neuronal stimulation by O-CST and patch-clamp detection, and single neuron patch-clamp stimulation and O-CST recording.
Figure 3: Optical imaging of the modulation of the neuron membrane potential induced by the O-CST device.
Figure 4: O-CST stimulation and recording of neurons and comparison with the MEA.
Figure 5: Raster plots and PSTH of the O-CST recording and comparison with the MEA.

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Acknowledgements

Financial support by Consorzio MIST E-R through Programma Operativo FESR 2007-2013 della Regione Emilia-Romagna– Attività I.1.1., MIUR through project PRIN 2009- 2009AZKNJ7 and EU FP7 Marie Curie ITN-316832 project OLIMPIA are acknowledged. We are grateful to P. Mei and T. Bonfiglioli from CNR-ISMN and to V. Biondo and R. D’Alpaos from E.T.C. for their valuable technical contribution. S. Ferroni and M. Caprini (for comments on the work), and A. Minardi (for DRG cell culture preparation), from the Department of Human and General Physiology of the University of Bologna, are gratefully acknowledged.

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Author notes

  1. Valentina Benfenati and Stefano Toffanin: These authors contributed equally to this work

Authors and Affiliations

  1. Consiglio Nazionale delle Ricerche (CNR), Istituto per la Sintesi Organica e la Fotoreattività (ISOF), via Gobetti, 101, 40129 Bologna, Italy

    Valentina Benfenati, Assunta Pistone, Anna Sagnella & Roberto Zamboni

  2. Consiglio Nazionale delle Ricerche (CNR), Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), via P. Gobetti 101, I-40129 Bologna, Italy

    Stefano Toffanin, Simone Bonetti, Giampiero Ruani, Davide Saguatti & Michele Muccini

  3. E.T.C. s.r.l., via P. Gobetti 101, I-40129 Bologna, Italy

    Guido Turatti, Andrea Stefani, Gianluca Generali & Michele Muccini

  4. Department of Neuroscience and Brain Technologies (NBT), Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genova, Italy

    Michela Chiappalone

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Contributions

V.B. defined the concept of the O-CST device, cultured DRG neurons, performed patch-clamp and optical read-out experiments, extracellular recording experiments, analysed and interpreted results. S.T. defined the concept of the O-CST device, performed optical imaging and optical read-out experiments, extracellular recording experiments, analysed and interpreted results. S.B. performed O-CST and MEA measurements. G.T. contributed to the fabrication of OFET devices and performed electrical measurements. A.P. prepared DRG cell culture and performed cell viability assays. M.C. performed elaboration and statistical analysis of O-CST and MEA data. A. Sagnella contributed to the fabrication of the OFET devices. A. Stefani contributed to the fabrication of the OFET devices. G.G. contributed to the fabrication of the OFET devices and performed electrical measurements. G.R. discussed and interpreted results. D.S. performed simulation of the O-CST device electric field and electrostatic potential. R.Z. discussed the concept of the O-CST device. M.M. defined the concept of the O-CST device, discussed and interpreted results, coordinated and supervised the entire work and wrote the manuscript.

Corresponding authors

Correspondence to Valentina Benfenati, Stefano Toffanin or Michele Muccini.

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Benfenati, V., Toffanin, S., Bonetti, S. et al. A transparent organic transistor structure for bidirectional stimulation and recording of primary neurons. Nature Mater 12, 672–680 (2013). https://doi.org/10.1038/nmat3630

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