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Monolithic three-dimensional neural probes from deterministic rolling of soft electronics

Abstract

Cognition and behaviour rely on coordinated activity from neural circuits distributed across three dimensions. However, typical probes for recording neural activity in the brain are limited to two-dimensional interfacing due to the planar semiconductor fabrication process. Here we report a rolling-of-soft-electronics approach to create monolithic three-dimensional (3D) neural probes with high scalability and design flexibility. Compared with previous stacking or assembly methods, the approach directly transforms a planar device into a 3D probe by leveraging the softness of flexible electrodes. The electrode shanks are initially fabricated in a single plane and then connected to a flexible spacer. By varying the features of planar design, such as shank pitch and spacer layer thickness, the device can then be deterministically rolled into versatile 3D probe designs containing hundreds of electrodes. With the system, we demonstrate single-unit spike recording in vivo in rodent and non-human primate models. We also show that the probe can provide microscopy-like 3D spatiotemporal mapping of spike activities in the rodent visual cortex, with five-week-long recording stability and promising 3D decoding performance of visual orientation.

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Fig. 1: ROSE leads to monolithic 3D neural probes.
Fig. 2: The ROSE approach leverages conventional microelectronic design flexibility and is highly deterministic.
Fig. 3: Insertion dynamics of ROSE probes and robustness of aid-free insertion.
Fig. 4: Demonstration of high-yield, microscopy-like 3D recordings and their durability from ROSE probes in rodents in vivo.
Fig. 5: 3D ROSE probes facilitate the neural decoding of visual orientations in an awake mouse.
Fig. 6: Intracortical recording using large-scale ROSE probes results in high-yield SU spike detection in a rhesus monkey cortex.

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Data availability

Animal electrophysiology data that support the findings of this study are available via Zenodo at https://doi.org/10.5281/zenodo.15498935 (ref. 81). All other datasets generated during and/or analysed during the study are available from the corresponding authors upon reasonable request. Source data are provided with this paper.

Code availability

The custom Python scripts used to analyse the neural signals and visualize the spike activities are available via GitHub at https://github.com/qiangy0819/ROSE_process.git. Code for extended analyses is available upon reasonable request.

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Acknowledgements

We acknowledge support from NIH award nos. R21EY030710 and U01NS123668, NSF award no. 2347978 and funds from Dartmouth College. S. Wang acknowledges support from the NSF CAREER award no. CMMI-1847062 and the Oklahoma Center for Advancement of Science & Technology grant no. HR18-085. X.T.C. acknowledges NINDS R01NS136622, R01 NS102725 and U01 NS113279. C.C. is supported by an NIH/NINDS K99/R00 NS092972, NIH/NINDS R01 NS122969, the Brain and Behavior Research Foundation, the Moorman-Simon Interdisciplinary Career Development Professorship and the Whitehall Foundation. T.L.M. acknowledges financial support from NIH/NIA R01 AG068168 and NIH/NINDS R56 NS112207.

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Authors and Affiliations

Authors

Contributions

H.F., S. Wang and X.T.C. supervised this work. W.G., K.J.S., Y.Q. and H.F. conceived the original concept of ROSE. W.G. and K.J.S. conducted the preliminary device optimization, fabrication and ROSE assembly. Y.Q. and T.B. designed and prototyped the MagMatrix board. Y.S., Y.Q. and J.R. further optimized the device design and fabrication for in vivo experiments. W.G., Y.Q., Y.S., G.L. and D.J. performed the device characterizations, mathematical modelling (offsets) and insertion dynamics testing. Y.Q., D.J., D.S. and W.G. performed the in vivo electrophysiology. Y.Q. and D.J. conducted the neural data processing and decoding analysis. D.J., D.S., S. Wu, A.I., J.-Y.L., D.L.R., M.M., T.L.M., A.N.K., R.K., P.A. and C.C. performed the animal surgeries and experiments. D.S. and V.D. performed the histological studies through immunohistochemistry and confocal fluorescence imaging. S.V., G.L., W.G. and S. Wang performed the structural and mechanical modelling of the ROSE shanks, including insertion force dynamics (S.V. and S. Wang), micromotion and twisting analysis (G.L.), and maximum principal strain (W.G.). Y.Q., W.G., D.S., K.J.S., D.J., Y.S., S. Wang and H.F. co‑wrote the manuscript. Y.Q., W.G. and D.S. prepared the figures. W.G. led the research in the original submission of the manuscript, and Y.Q. led the revision work. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Xinyan Tracy Cui, Shuodao Wang or Hui Fang.

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Competing interests

H.F., W.G., Y.Q. and K.J.S. are inventors on patent application US 19/058,657 filed by Dartmouth College that covers the 3D ROSE probe technology reported in this manuscript. H.F., Y.Q. and K.J.S. are inventors on patent US 11417987B2 covering the MagMatrix connector technology reported in this manuscript. The other authors declare no competing interests.

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Supplementary Figs. 1–40, Tables 1–6 and Notes 1–8.

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ROSE probe insertion process and synchronized force dynamic.

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3D SU firing map under one visual stimulation trial.

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Qiang, Y., Gu, W., Jang, D. et al. Monolithic three-dimensional neural probes from deterministic rolling of soft electronics. Nat Electron 8, 721–737 (2025). https://doi.org/10.1038/s41928-025-01431-0

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