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Electrolyte-gated transistors for enhanced performance bioelectronics

Nature Reviews Methods Primers volume 1, Article number: 66 (2021) Cite this article

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Abstract

Electrolyte-gated transistors (EGTs), capable of transducing biological and biochemical inputs into amplified electronic signals and stably operating in aqueous environments, have emerged as fundamental building blocks in bioelectronics. In this Primer, the different EGT architectures are described with the fundamental mechanisms underpinning their functional operation, providing insight into key experiments including necessary data analysis and validation. Several organic and inorganic materials used in the EGT structures and the different fabrication approaches for an optimal experimental design are presented and compared. The functional bio-layers and/or biosystems integrated into or interfaced to EGTs, including self-organization and self-assembly strategies, are reviewed. Relevant and promising applications are discussed, including two-dimensional and three-dimensional cell monitoring, ultra-sensitive biosensors, electrophysiology, synaptic and neuromorphic bio-interfaces, prosthetics and robotics. Advantages, limitations and possible optimizations are also surveyed. Finally, current issues and future directions for further developments and applications are discussed.

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Fig. 1: EGTs for enhanced bioelectronics.
Fig. 2: Typical organic materials used for EGTs.
Fig. 3: Typical inorganic semiconductors used for EGTs.
Fig. 4: Fabrication of EGTs.
Fig. 5: Integration of bio-layers in EGTs.
Fig. 6: Representative electrical characteristics of EGTs.
Fig. 7: Three-dimensional cell monitoring, ultra-sensitive biosensors and in vivo electrophysiology using EGTs.
Fig. 8: Synaptics and neuromorphics with EGTs.

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Acknowledgements

F.T and L.T. acknowledge financial support from the European Union, Italian Government and Lombardia Region for the project BIOSCREEN (POR FESR 2014-2020, ID number 1831459, CUP E81B20000320007). F.T., E.M. and L.T. acknowledge financial support from the European Commission for the project SiMBiT (Horizon 2020 ICT, contract number 824946). D.Z.A. was supported by a Biotechnology Training (Grant No. NIH T32GM008347). G.G.M. acknowledges support from H2020-EU-FET Open MITICS (964677).

Author information

Authors and Affiliations

  1. Department of Information Engineering, University of Brescia, Brescia, Italy

    Fabrizio Torricelli

  2. Department of Chemical Engineering & Materials Science, University of Minnesota, Minneapolis, MN, USA

    Demetra Z. Adrahtas & C. Daniel Frisbie

  3. Department of Chemical Engineering, Stanford University, Stanford, CA, USA

    Zhenan Bao

  4. Laboratory of Organic Electronics, Department of Science and Technology, Linköping University, Norrköping, Sweden

    Magnus Berggren

  5. Dipartimento di Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, Modena, Italy

    Fabio Biscarini & Carlo A. Bortolotti

  6. Center for Translational Neurophysiology of Speech and Communication, Istituto Italiano di Tecnologia, Ferrara, Italy

    Fabio Biscarini

  7. Department of Electrical and Electronic Engineering, University of Cagliari, Cagliari, Italy

    Annalisa Bonfiglio & Andrea Spanu

  8. Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland

    Eleonora Macchia

  9. Electrical Engineering Division, Department of Engineering, University of Cambridge, Cambridge, UK

    George G. Malliaras

  10. Physical Sciences and Engineering Division, KAUST Solar Center (KSC), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia

    Iain McCulloch

  11. Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK

    Iain McCulloch & Maximilian Moser

  12. Department of Chemistry & Biochemistry, University of California Santa Barbara, Santa Barbara, CA, USA

    Thuc-Quyen Nguyen

  13. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK

    Róisín M. Owens

  14. Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA

    Alberto Salleo

  15. Department of Chemistry, University of Bari ‘Aldo Moro’, Bari, Italy

    Luisa Torsi

Authors
  1. Fabrizio Torricelli
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  2. Demetra Z. Adrahtas
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  3. Zhenan Bao
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  4. Magnus Berggren
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  5. Fabio Biscarini
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  6. Annalisa Bonfiglio
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  7. Carlo A. Bortolotti
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  8. C. Daniel Frisbie
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  9. Eleonora Macchia
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  10. George G. Malliaras
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  15. Alberto Salleo
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  16. Andrea Spanu
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  17. Luisa Torsi
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Contributions

Introduction (F.T., C.D.F. and D.Z.A.); Box 1 (F.B. and C.A.B.); Experimentation (T.-Q.N., I.M., M.M., C.D.F., D.Z.A., L.T., E.M., F.B. and C.A.B.); Box 2 (M.B.), Box 3 (A.B. and A. Spanu); Results (F.T.); Applications (R.M.O., L.T., G.G.M., A. Salleo and Z.B); Reproducibility and data deposition (F.T. and G.G.M.); Limitations and optimizations (F.T., F.B. and C.A.B.); Outlook (L.T.); Overview of the Primer (F.T. and L.T.). All authors commented on the paper.

Corresponding authors

Correspondence to Fabrizio Torricelli or Luisa Torsi.

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Nature Reviews Methods Primers thanks S. Dasgupta, H. Kawarada, Q. Wan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Glossary

Bio-layer

A biological layer made with biological entities such as, for example, antibodies, peptides, DNA, RNA, enzymes, cells, tissues or organs.

Intermolecular hopping events

Charge transport mechanisms taking place between various parts of molecules and polymers.

Hole injection

The transfer of holes from an electrode to a semiconductor.

HOMO

(Highest occupied molecular orbital). A type of molecular orbital.

Polarons

Fermionic quasiparticles due to the strong interaction between electrons and atoms in a solid material. When electrons move in a dielectric crystal, the atoms displace from their equilibrium positions to screen the electronic charges.

Atomic layer deposition

A vacuum deposition method based on sequential use of one or more volatile compounds that react and/or decompose on the substrate surface, producing a deposit of a thin-film layer.

Sputtering

A method used for the deposition of metals, insulators and semiconductors. In a vacuum chamber, a solid material (named target) is bombarded by energetic particles of a plasma or gas. The microscopic particles ejected from its surface deposit on a substrate.

Oxygen plasma

A plasma for treatment of a surface that is an effective, economical, environmentally safe method for critical cleaning.

Ozone cleaning

A cleaning process of surfaces based on photochemical reactions involving ultraviolet light, oxygen and the material on the surface of the substrate.

Shadow masking

A technique using a metal, silicon or plastic sheet with suitably designed openings coupled to a substrate. A material deposited over the mask can reach the substrate only in the opening regions, thus defining a pattern according to the design of the mask.

Polarizable

Characterized by a charge separation at the electrode–electrolyte interface and electrically equivalent to a capacitor.

Non-polarizable

Characterized by no charge separation and electrically equivalent to a resistor.

Electrocardiography

The process of recording the electrical signals of the heart.

Electromyography

The process of recording the electrical signals of skeletal muscles.

Electro-oculography

The process of recording the electrical signals of eye.

Spheroids

Dense three-dimensional assemblies of cells grown in gels composed of extracellular matrix.

Point-of-care

Medical diagnostic testing at the place and time of the patient care.

Memristive

Relating to a non-linear two-terminal electrical component linking magnetic flux and electric charge.

Gate voltage scanning

A method in which the gate voltage is swept from an initial value to a final value, typically with a constant voltage and time step size.

Plasma

A gas of ions with one or more orbital electrons stripped and free electrons.

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Torricelli, F., Adrahtas, D.Z., Bao, Z. et al. Electrolyte-gated transistors for enhanced performance bioelectronics. Nat Rev Methods Primers 1, 66 (2021). https://doi.org/10.1038/s43586-021-00065-8

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