Abstract
Biological systems operate across distributed regions with fast, localized dynamics, yet existing biointerfaces fall short of providing both high spatiotemporal precision and the ability to dynamically target any region without disturbing surrounding tissue. Here we present an in vivo deep-tissue light source based on focused ultrasound scanning of mechanoluminescent nanotransducers circulating through the vasculature. We demonstrate the programmability of this approach in tissue-mimicking phantoms and the endogenous circulatory system of animals, where tunable spatial resolution and dynamic light patterning are achieved. We validate the functionality of the ultrasound-scanning light source in opsin-expressing neurons through electrophysiological recordings and immunostaining in both the brain and the spinal cord. We showcase dynamic three-dimensional brain targeting and temporally resolved behavioural control in freely moving animals via the ultrasound-scanning in vivo light source. This non-invasive deep-tissue light source offers a versatile strategy for body-wide optical interfacing.
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Data availability
The data that support the findings of this study are available within this article and its Supplementary Information. Source data are provided with this paper.
Code availability
The custom MATLAB code used in this study for spike sorting is available at https://github.com/ShanJiang1233/Jiang_2025 and is archived at Zenodo at https://doi.org/10.5281/zenodo.18609351 (ref. 65).
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Acknowledgements
We thank A. Deniz Guler for donation of D1–cre mice and the University of Virginia School of Medicine Research Histology Core Facility for help with the preparation of histologic specimens. Part of the confocal microscopy imaging was performed at the Stanford Wu Tsai Neuroscience Microscopy Service. G.H. acknowledges three awards by NIH (5R00AG056636-04, 1R34NS127103-01 and R01NS126076-01), a National Science Foundation (NSF) CAREER Award (2045120), an NSF EAGER Award (2217582), a Rita Allen Foundation Scholars Award, a Beckman Technology Development Grant, a grant from the Focused Ultrasound Foundation, a gift from the Spinal Muscular Atrophy Foundation, a gift from the Pinetops Foundation, two seed grants from the Wu Tsai Neurosciences Institute, two seed grants from the Bio-X Initiative of Stanford University and a Synthetic Neurobiology Grant of Stanford University. H.S. acknowledges four awards by NIH (R01AG072430, R56 AG077720, R01AG085359 and R01NS123069). S.J. acknowledges support by the BRAIN Postdoctoral Fellowship from the University of Virginia. M.G.M. and N.J.R. acknowledge support by Bio-X Graduate Student Fellowships. M.G.M. and N.J.R. acknowledge support by the NSF Graduate Research Fellowships Program (award 1656518). X.W. acknowledges support by a Stanford Graduate Fellowship. X.C. acknowledges four awards by NIH (R01NS129834, R01DA059602, R01MH116904 and R01DA045664). Some illustrations were created with BioRender.com.
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S.J., X.C., J.D., H.S. and G.H. conceived and designed the project; S.J., M.G.M. and F.Y. synthesized MLNTs; F.Y. and H.C. performed the structure and morphology characterizations; S.J., F.Y. and N.J.R. performed the optical characterizations; S.J., M.G.M. and N.J.R. performed the pressure mapping; S.J. and X.W. performed imaging of the mechanoluminescence emission from the mouse; S.J. and M.G.M performed in vivo fibre photometry; S.J. performed the electrophysiological recording; S.J. performed the immunostaining and confocal microscopy imaging; S.J. and S.Z. performed the evaluation of recharging efficiency; Y.Z. and Q.Z. fabricated and validated the wearable transducer; S.J. designed the head-mounted system; S.J. and S.S.H. performed the behaviour assays; S.J., M.G.M., S.S.H. and L.C. performed the biocompatibility studies. S.J., F.Y., L.C., H.S. and G.H. analysed the data. All authors contributed to the writing of the paper.
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Extended data
Extended Data Fig. 1 Pressure mapping of the FUS transducers operating at different frequencies.
a-d, Acoustic pressure fields in both the lateral (x–y plane at z0 = 0, i) and axial (y–z plane, at x0 = 0, ii) planes for a 0.65-MHz transducer (a), 1.5-MHz transducer (b), 3.3-MHz transducer (c), and 5.7-MHz transducer (d). In each panel, subpanels iii and iv display the corresponding spatial pressure profiles across the dashed lines in i and ii, respectively. FWHM was used to quantify the lateral resolution, while the depth of focus (DOF), defined as the −6 dB pressure width, was used to quantify the axial resolution.
Extended Data Fig. 2 Validating the efficacy of the ultrasound-scanning in vivo light source with c-Fos immunostaining.
a, Schematic illustration of the FUS-mediated light source in the M1 region. b, Representative immunostaining images of ChR2-YFP and c-Fos in the M1 region under different experimental conditions. c, Statistical analysis of the c-Fos cell density in the M1 region across different experimental groups. d, Schematic illustration of the FUS-mediated light source in the vDG. e, Representative immunostaining images of ChR2-YFP and c-Fos in the vDG under different experimental conditions. f, Statistical analysis of the c-Fos cell density in the vDG across different experimental groups. Scale bars represent 40 µm in b and 80 µm in e. All data are presented as mean ± s.d. with data points shown for n = 3 mice in each group. Statistical significance and P values are determined by ordinary one-way ANOVA: **P < 0.01, ****P < 0.0001.
Extended Data Fig. 3 Biocompatibility assessment of the ultrasound-scanning light source.
a, e, Representative immunostaining images of the M1 region 1 week (a) and 4 weeks (e) post-procedure under different experimental conditions. b, f, Statistical analysis of neuronal density 1 week (b) and 4 weeks (f) post-procedure. c, g, Statistical analysis of GFAP area 1 week (c) and 4 weeks (g) post-procedure. d, h, Statistical analysis of Iba1 area 1 week (d) and 4 weeks (h) post-procedure. All scale bars represent 50 µm. All data are presented as mean ± s.d. with data points shown for each animal from n = 4 mice in each group. Statistical significance and P values are determined by ordinary one-way ANOVA: P ≥ 0.05 (n.s.).
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Supplementary Video Legends 1–4, Note 1, Figs. 1–31, Table 1 and refs. 1–5.
Supplementary Video 1 (download AVI )
Dynamic ultrasound-mediated photostimulation of the left striatum in freely moving D1–Cre::ChR2–YFP mouse.
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Dynamic ultrasound-mediated photostimulation of the right striatum in freely moving D1–Cre::ChR2–YFP mouse.
Supplementary Video3 (download AVI )
Dynamic ultrasound-mediated photostimulation of the left striatum in freely moving A2a–Cre::ChR2–YFP mouse.
Supplementary Video4 (download AVI )
Dynamic ultrasound-mediated photostimulation of the right striatum in freely moving A2a–Cre::ChR2–YFP mouse.
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Jiang, S., Malinao, M.G., Yang, F. et al. An ultrasound-scanning in vivo light source. Nat. Mater. (2026). https://doi.org/10.1038/s41563-026-02556-z
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DOI: https://doi.org/10.1038/s41563-026-02556-z


