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Tapered fibertrodes for optoelectrical neural interfacing in small brain volumes with reduced artefacts

Abstract

Deciphering the neural patterns underlying brain functions is essential to understanding how neurons are organized into networks. This deciphering has been greatly facilitated by optogenetics and its combination with optoelectronic devices to control neural activity with millisecond temporal resolution and cell type specificity. However, targeting small brain volumes causes photoelectric artefacts, in particular when light emission and recording sites are close to each other. We take advantage of the photonic properties of tapered fibres to develop integrated ‘fibertrodes’ able to optically activate small brain volumes with abated photoelectric noise. Electrodes are positioned very close to light emitting points by non-planar microfabrication, with angled light emission allowing the simultaneous optogenetic manipulation and electrical read-out of one to three neurons, with no photoelectric artefacts, in vivo. The unconventional implementation of two-photon polymerization on the curved taper edge enables the fabrication of recoding sites all around the implant, making fibertrodes a promising complement to planar microimplants.

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Fig. 1: Fabrication process.
Fig. 2: Electrical characterization and extracellular recordings.
Fig. 3: Light emission properties in quasi-transparent solutions and related Monte Carlo simulations in scattering brain tissue.
Fig. 4: Light-induced photoelectric noise in PBS.
Fig. 5: In vivo test of the fibertrode.
Fig. 6: Scalability of the 2PP-based patterning process.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding authors on reasonable request and are available in the Zenodo repository (https://doi.org/10.5281/zenodo.6477861). Data on the optrode fabrication and in vitro optical measurements are available from B.S., A.B., L.S., F. Pisanello and M.D.V. Data on the in vivo use of tapered fibres are available from B.S., R.T.P., B.L.S. and F. Pisanello.

Code availability

The scripts related to the Monte Carlo simulations used in the current study are available from the corresponding authors on reasonable request and are available in the Zenodo repository (https://doi.org/10.5281/zenodo.6477861).

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Acknowledgements

B.S., A.B., M.B., F. Pisano and F. Pisanello acknowledge funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (no. 677683); M.P. and M.D.V. acknowledge funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (no. 692943). M.B., M.D.V. and F.Pisanello acknowledge funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (no. 966674). F. Pisano, M.D.V. and F. Pisanello acknowledge funding from the European Union’s Horizon 2020 research and innovation programme (no. 101016787). L.S., M.D.V. and B.L.S. are funded by the US National Institutes of Health (U01NS094190). M.P., L.S., F. Pisanello, M.D.V. and B.L.S. are funded by the US National Institutes of Health (1UF1NS108177-01). A.B., F. Pisanello and M.D.V. also acknowledge funding from the European Union’s Horizon 2020 research and innovation programme (no. 828972). We also acknowledge J. Lee for help setting up the optrode fibre launch system.

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Contributions

A.B., B.S., M.P. and R.T.P. equally contributed to this work. A.B., M.P., M.B., A.R., M.D.V., F. Pisano and F. Pisanello developed the 2PP system and the related fibertrode. L.S., B.S., M.P., A.Q., F. Pisano, M.D.V. and F. Pisanello developed the FIB fabrication protocol and the related fibertrode. B.S., A.B., M.P., M.B. and F. Pisanello performed the optoelectrical characterization of the probes. B.S. and R.T.P. performed the in vivo experiments. B.S., A.B., M.P., F. Pisano, F. Pisanello, R.T.P., B.L.S., J.A.A. and M.D.V. analysed and discussed the in vivo data. B.L.S., R.T.P., B.S., D.D.L., F.D.N. and F. Pisanello developed the in vivo experiment protocols. A.B., B.S., L.S., F. Pisanello, M.D.V., B.L.S. and J.A.A. wrote the manuscript and prepared the figures with contributions from all authors. M.D.V., B.L.S., J.A.A. and F. Pisanello conceived the study and jointly supervised the work.

Corresponding authors

Correspondence to Barbara Spagnolo, Antonio Balena, Massimo De Vittorio or Ferruccio Pisanello.

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Competing interests

L.S., B.L.S., M.D.V. and F. Pisanello are founders of and hold private equity in Optogenix, a company that develops, produces and sells technologies to deliver light into the brain. Tapered fibres commercially available from Optogenix were used as tools in the research. The remaining authors declare no competing interests. F. Pisano and M.P. have been employed by OptogeniX. OptogeniX did not fund the research described in this work.

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Spagnolo, B., Balena, A., Peixoto, R.T. et al. Tapered fibertrodes for optoelectrical neural interfacing in small brain volumes with reduced artefacts. Nat. Mater. 21, 826–835 (2022). https://doi.org/10.1038/s41563-022-01272-8

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