Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Enhancement-mode ion-based transistor as a comprehensive interface and real-time processing unit for in vivo electrophysiology

Nature Materials volume 19, pages 679–686 (2020)Cite this article

Subjects

Abstract

Bioelectronic devices must be fast and sensitive to interact with the rapid, low-amplitude signals generated by neural tissue. They should also be biocompatible and soft, and should exhibit long-term stability in physiologic environments. Here, we develop an enhancement-mode, internal ion-gated organic electrochemical transistor (e-IGT) based on a reversible redox reaction and hydrated ion reservoirs within the conducting polymer channel, which enable long-term stable operation and shortened ion transit time. E-IGT transient responses depend on hole rather than ion mobility, and combine with high transconductance to result in a gain–bandwidth product that is several orders of magnitude above that of other ion-based transistors. We used these transistors to acquire a wide range of electrophysiological signals, including in vivo recording of neural action potentials, and to create soft, biocompatible, long-term implantable neural processing units for the real-time detection of epileptic discharges. E-IGTs offer a safe, reliable and high-performance building block for chronically implanted bioelectronics, with a spatiotemporal resolution at the scale of individual neurons.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Operating mechanism, structure, and steady-state characteristics of an e-IGT.
Fig. 2: PEDOT:PSS–PEI composite creates long-term, stable, volumetric capacitance for the operation of an enhancement-mode transistor.
Fig. 3: High-speed transient response of an e-IGT is a function of hole rather than ion mobility.
Fig. 4: E-IGTs have a high gain–bandwidth product and create low-leakage, effective integrated circuits.
Fig. 5: E-IGTs enable high-quality electrophysiological signal acquisition across a broad range of frequencies and amplitudes.
Fig. 6: E-IGTs in combination with d-IGTs enable real-time non-linear signal rectification for the accurate detection of epileptic discharges in vivo.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Information. All source files and experimental data are freely and publicly available at www.dion.ee.columbia.edu. Additional data related to this paper may be requested from the authors.

References

  1. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 1–16 (2017).

    CAS  Google Scholar 

  2. Jeong, J. W. et al. Soft materials in neuroengineering for hard problems in neuroscience. Neuron 86, 175–186 (2015).

    CAS  Google Scholar 

  3. Someya, T., Bao, Z. & Malliaras, G. G. The rise of plastic bioelectronics. Nature 540, 379–385 (2016).

    CAS  Google Scholar 

  4. Spyropoulos, G. D., Gelinas, J. N. & Khodagholy, D. Internal ion-gated organic electrochemical transistor: a building block for integrated bioelectronics. Sci. Adv. 5, eaau7378 (2019).

    CAS  Google Scholar 

  5. Fang, H. et al. Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems. Proc. Natl Acad. Sci. USA 113, 11682–11687 (2016).

    CAS  Google Scholar 

  6. Kim, D.-H. et al. Stretchable and foldable silicon integrated circuits. Nature 320, 507–511 (2008).

    CAS  Google Scholar 

  7. Cho, J. H. H. et al. High-capacitance ion gel gate dielectrics with faster polarization response times for organic thin film transistors. Adv. Mater. 20, 686–690 (2008).

    CAS  Google Scholar 

  8. Kim, S. H. et al. Electrolyte-gated transistors for organic and printed electronics. Adv. Mater. 25, 1822–1846 (2013).

    CAS  Google Scholar 

  9. Panzer, M. J. & Frisbie, C. D. Polymer electrolyte-gated organic field-effect transistors: low-voltage, high-current switches for organic electronics and testbeds for probing electrical transport at high charge carrier density. J. Am. Chem. Soc. 129, 6599–6607 (2007).

    CAS  Google Scholar 

  10. Zare Bidoky, F. et al. Sub-3 V ZnO electrolyte-gated transistors and circuits with screen-printed and photo-crosslinked ion gel gate dielectrics: new routes to improved performance. Adv. Funct. Mater. https://doi.org/10.1002/adfm.201902028 (2019).

    Google Scholar 

  11. Song, E. et al. Flexible electronic/optoelectronic microsystems with scalable designs for chronic biointegration. Proc. Natl Acad. Sci. USA 116, 15398–15406 (2019).

    Google Scholar 

  12. Rivnay, J. et al. Organic electrochemical transistors. Nat. Rev. Mater. 3, 17086 (2018).

    CAS  Google Scholar 

  13. Giovannitti, A. et al. Controlling the mode of operation of organic transistors through side-chain engineering. Proc. Natl Acad. Sci. USA 113, 12017–12022 (2016).

    CAS  Google Scholar 

  14. Nielsen, C. B. et al. Molecular design of semiconducting polymers for high-performance organic electrochemical transistors. J. Am. Chem. Soc. 138, 10252–10259 (2016).

    CAS  Google Scholar 

  15. Schmode, P. et al. High-performance organic electrochemical transistors based on conjugated polyelectrolyte copolymers. Chem. Mater. 31, 5286–5295 (2019).

    CAS  Google Scholar 

  16. Bernards, D. A. & Malliaras, G. G. Steady-state and transient behavior of organic electrochemical transistors. Adv. Funct. Mater. 17, 3538–3544 (2007).

    CAS  Google Scholar 

  17. Stavrinidou, E. et al. Direct measurement of ion mobility in a conducting polymer. Adv. Mater. 25, 4488–4493 (2013).

    CAS  Google Scholar 

  18. Khodagholy, D. et al. High speed and high density organic electrochemical transistor arrays. Appl. Phys. Lett. 99, 163304 (2011).

    Google Scholar 

  19. Crispin, X. et al. The origin of the high conductivity of poly(3,4-ethylenedioxythiophene)−poly(styrenesulfonate) (PEDOT:PSS) plastic electrodes. Chem. Mater. 18, 4354–4360 (2006).

    CAS  Google Scholar 

  20. Spyropoulos, G. D. et al. Organic and perovskite solar modules innovated by adhesive top electrode and depth-resolved laser patterning. Energy Environ. Sci. 9, 2302–2313 (2016).

    CAS  Google Scholar 

  21. Zhou, Y. et al. A universal method to produce low–work function electrodes for organic electronics. Org. Electron. 873, 327–332 (2012).

    Google Scholar 

  22. Lin, Z. et al. A work-function tunable polyelectrolyte complex (PEI:PSS) as a cathode interfacial layer for inverted organic solar cells. J. Mater. Chem. A 2, 7788–7794 (2014).

    CAS  Google Scholar 

  23. Xuan, Y., Sandberg, M., Berggren, M. & Crispin, X. An all-polymer-air PEDOT battery. Org. Electron. Phys. Mater. Appl. 13, 632–637 (2012).

    CAS  Google Scholar 

  24. Van de Burgt, Y. et al. A non-volatile organic electrochemical device as a low-voltage artificial synapse for neuromorphic computing. Nat. Mater. 16, 414–418 (2017).

    Google Scholar 

  25. Zozoulenko, I. et al. Polarons, bipolarons, and absorption spectroscopy of PEDOT. ACS Appl. Polym. Mater. 1, 83–94 (2019).

    CAS  Google Scholar 

  26. Ravi Kumar, M. N. V. A review of chitin and chitosan applications. React. Funct. Polym. 46, 1–27 (2000).

    Google Scholar 

  27. Jiang, H. L. et al. Chitosan-graft-polyethylenimine as a gene carrier. J. Control. Release 117, 273–280 (2007).

    CAS  Google Scholar 

  28. Khodagholy, D. et al. In vivo recordings of brain activity using organic transistors. Nat. Commun. 4, 1575 (2013).

    Google Scholar 

  29. Khodagholy, D. et al. High transconductance organic electrochemical transistors. Nat. Commun. 4, 2133 (2013).

    Google Scholar 

  30. Rivnay, J. et al. High-performance transistors for bioelectronics through tuning of channel thickness. Sci. Adv. 1 e1400251 (2015).

    Google Scholar 

  31. Inal, S., Malliaras, G. G. & Rivnay, J. Benchmarking organic mixed conductors for transistors. Nat. Commun. 8, 1767 (2017).

    Google Scholar 

  32. Khodagholy, D. et al. NeuroGrid: recording action potentials from the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).

    CAS  Google Scholar 

  33. Krook-Magnuson, E., Gelinas, J. N., Soltesz, I. & Buzsáki, G. Neuroelectronics and biooptics: closed-loop technologies in neurological disorders. JAMA Neurol. 72, 823–829 (2015).

    Google Scholar 

  34. Choi, H. H., Cho, K., Frisbie, C. D., Sirringhaus, H. & Podzorov, V. Critical assessment of charge mobility extraction in FETs. Nat. Mater. 17, 2–7 (2018).

    CAS  Google Scholar 

  35. Rivnay, J. et al. Structural control of mixed ionic and electronic transport in conducting polymers. Nat. Commun. 7, 11287 (2016).

    Google Scholar 

  36. Podzorov, V. Organic single crystals: addressing the fundamentals of organic electronics. MRS Bull. 38, 15–24 (2013).

    Google Scholar 

  37. Crone, B. et al. Large-scale complementary integrated circuits based on organic transistors. Nature 403, 521 (2000).

    CAS  Google Scholar 

  38. Kim, Y. et al. A bioinspired flexible organic artificial afferent nerve. Science 360, 998–1003 (2018).

    CAS  Google Scholar 

  39. Sessolo, M. et al. Easy-to-fabricate conducting polymer microelectrode arrays. Adv. Mater. 25, 2135–2139 (2013).

    CAS  Google Scholar 

  40. Khodagholy, D., Gelinas, J. N. & Buzsáki, G. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science 372, 369–372 (2017).

    Google Scholar 

  41. Peyrache, A., Battaglia, F. P. & Destexhe, A. Inhibition recruitment in prefrontal cortex during sleep spindles and gating of hippocampal inputs. Proc. Natl Acad. Sci. USA 108, 17207–17212 (2011).

    CAS  Google Scholar 

  42. Khan, F., Tare, R. S., Oreffo, R. O. C. & Bradley, M. Versatile biocompatible polymer hydrogels: scaffolds for cell growth. Angew. Chem. Int. Ed. 48, 978–982 (2009).

    CAS  Google Scholar 

  43. Buzsaki, G. Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Hippocampus 25, 1073–1188 (2015).

    Google Scholar 

  44. Morrell, M. J. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77, 1295–1304 (2011).

    Google Scholar 

  45. González Otárula, K. A., Mikhaeil-Demo, Y., Bachman, E. M., Balaguera, P. & Schuele, S. Automated seizure detection accuracy for ambulatory EEG recordings. Neurology 92, e1540–e1546 (2019).

    Google Scholar 

  46. Buzsáki, G., Anastassiou, C. A. & Koch, C. The origin of extracellular fields and currents—EEG, ECoG, LFP and spikes. Nat. Rev. Neurosci. 13, 407–420 (2012).

    Google Scholar 

  47. Gelinas, J. N., Khodagholy, D., Thesen, T., Devinsky, O. & Buzsáki, G. Interictal epileptiform discharges induce hippocampal–cortical coupling in temporal lobe epilepsy. Nat. Med. 22, 641–648 (2016).

    CAS  Google Scholar 

  48. Inal, S. et al. A high transconductance accumulation mode electrochemical transistor. Adv. Mater. 26, 7450–7455 (2014).

    CAS  Google Scholar 

  49. Viventi, J. et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nat. Neurosci. 14, 1599–1605 (2011).

    CAS  Google Scholar 

  50. Zeglio, E. et al. Conjugated polyelectrolyte blends for electrochromic and electrochemical transistor devices. Chem. Mater. 27, 6385–6393 (2015).

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Columbia University, School of Engineering and Applied Science as well as Columbia University Medical Center, Department of Neurology and Institute for Genomic Medicine. The device fabrication was performed at Columbia Nano-Initiative (CNI) and at Cornell NanoScale Facility (CNF), a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (Grant ECCS-1542081). G.D.S. is supported through the Human Frontiers Postdoctoral Fellowship Program. This work was supported by an NIH grant (1U01NS108923-01), NSF CAREER award (1944415), CURE Taking Flight Award, Columbia School of Engineering. We thank M. Gonzalez, J. Yu, J. Vichiconti, Y. Borisenkov, P. Chow, C. Belfer, N. Ariel-Sternberg (CNI) and all Khodagholy and Gelinas laboratory members for their support.

Author information

Author notes

  1. These authors contributed equally: Claudia Cea, George D. Spyropoulos.

Authors and Affiliations

  1. Department of Electrical Engineering, Columbia University, New York, NY, USA

    Claudia Cea, George D. Spyropoulos, Patricia Jastrzebska-Perfect & Dion Khodagholy

  2. Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, USA

    José J. Ferrero & Jennifer N. Gelinas

  3. Department of Neurology, Columbia University Medical Center, New York, NY, USA

    Jennifer N. Gelinas

Authors
  1. Claudia Cea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George D. Spyropoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia Jastrzebska-Perfect
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José J. Ferrero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jennifer N. Gelinas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dion Khodagholy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.K., J.N.G. and C.C. conceived the project. C.C., D.K., G.D.S. and P.J. designed, developed, fabricated and characterized the materials and devices. C.C. and G.D.S. fabricated the neural probes for the rodent and human recordings. C.C. and G.D.S. performed the ECG and EMG recordings. D.K., C.C., J.J.F. and J.N.G. performed the electrophysiology in vivo rodent experiments and analysis. All authors contributed to writing the paper.

Corresponding authors

Correspondence to Jennifer N. Gelinas or Dion Khodagholy.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–18, Tables 1–2

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cea, C., Spyropoulos, G.D., Jastrzebska-Perfect, P. et al. Enhancement-mode ion-based transistor as a comprehensive interface and real-time processing unit for in vivo electrophysiology. Nat. Mater. 19, 679–686 (2020). https://doi.org/10.1038/s41563-020-0638-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41563-020-0638-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing