Abstract
Real-time detection of tissue oxygenation in the nervous system is crucial in neuroscience studies and clinical diagnostics. Complementary to blood oxygenation levels, the partial pressure of oxygen in brain tissue (\(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\)) plays a key role in regulating local neural activities and metabolism. Here we develop an implantable optoelectronic probe that wirelessly and continuously monitors \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) signals in the deep brain of freely moving rodents. The thin-film, microscale implant integrates a light-emitting diode and a photodetector, and is coated with an oxygen-sensitive phosphorescent film. Powered by a battery or an inductive coil, a miniaturized circuit is capable of recording and wirelessly transmitting \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) signals. The wireless micro-probe captures cerebral hypoxia states in mice in various scenarios, including altered inspired oxygen concentrations and acute ischaemia. In mouse models with seizures, the micro-probe associates temporal \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) variations in multiple brain regions with electrical stimulations applied to the hippocampus. Our probe and method offer important insights into neuroscience studies regarding neurometabolic coupling and pave the way for the clinical application of implantable wireless optoelectronic probes.
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Acknowledgements
This work is supported by the Beijing Municipal Natural Science Foundation (Z220015, to L.Y. and C.W.), the National Natural Science Foundation of China (NSFC) (52272277, to X.S.; 62005016, to H.D.; 8203000638, to G.Z.), the Science and Technology Innovation 2030-Major Project (2021ZD0201801, to G.Z.) and the Beijing Nova Program (20230484254, to H.D.). We thank Dr C. Pan, Prof. P. Yu and Prof. L. Mao for providing carbon-based electrodes for the electrochemical experiments.
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X.C., D.S., Z.L., B.Z., G.T., W.Z., Y.X. and X.F. performed the device design, fabrication and characterization. X.C., H.Z., Z.Y., Z.X. and H.D. designed and tested the circuits. X.C., P.W., Q.L., D.S., Y.D., C.W. and Y.W. designed and performed the biological experiments. P.W., C.W., L.Y., H.P., H.D., G.Z. and X.S. provided the tools and supervised the research. X.C., H.D. and X.S. wrote the paper in consultation with the other authors.
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Extended data
Extended Data Fig. 1
Schematic illustration of the process flow for fabricating the \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) sensing probe.
Extended Data Fig. 2 Optical properties of PtTFPP/PDMS films.
(a) Absorption and (b) PL emission spectra of PtTFPP with different mass concentrations mixed in PDMS films (thickness 10 μm). (c) Peak emissions and absorptions as a function of PtTFPP mass concentrations.
Extended Data Fig. 3 Images and optoelectronic properties of the InGaN violet LED.
(a) Microscopic images of a violet LED with (right) and without (left) electroluminescence. (b) The LED’s current–voltage characteristic curve. (c) The LED’s external quantum efficiencies (EQEs) as a function of currents.
Extended Data Fig. 4 Images and optoelectronic properties of the InGaP photodetector.
(a) Transmission spectra of a polyimide film (thickness 8 μm) and a dielectric filter. (b) Images of InGaP detectors with (lower) and without (upper) the filter. (c) External quantum efficiency (EQE) spectra for InGaP detectors with and without coatings of polyimide and the filter. (d) Current–voltage curves of an InGaP detector under different irradiance at 635 nm. (e) Photocurrent response of a detector coated with a filter measured at 405 nm and 635 nm illuminations. (f) Photocurrent response of a detector with and without filter coatings under 405 nm illumination.
Extended Data Fig. 5
Dynamic change of \(F_{{{\mathrm{i}}{\mathrm{O}}_2}}\) (top) and \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) results (bottom) recorded by our wireless micro-probe, in comparison with the data simultaneously detected by a carbon-based electrochemical electrode37.
Extended Data Fig. 6 Numerical simulation of O2 transport in brain tissue.
(a) 2D schematic model showing a PtTFPP/PDMS-based oxygen-sensitive film and capillaries within the brain tissue. (b) (top) Dynamic oxygen consumption rate (OCR) imported into the model, and (bottom) the corresponding O2 pressure (\(p_{{\mathrm{O}}_2}\)) calculated in the PtTFPP/PDMS film. (c) Distributions of \(p_{{\mathrm{O}}_2}\) in the tissue during (i) basal and (ii) hypoxia conditions.
Extended Data Fig. 7 Measurement of tissue blood oxygen saturation (\(S_{{\mathrm{t}}{{\mathrm{O}}_2}}\)) in the hippocampus of mice using a fibre-based setup.
(a) 3D schematic model showing positions of the two fibers and the stimulating electrode implanted in the ipsilateral hippocampus of mice (CA3 and CA1, respectively). One fiber couples to two LED sources emitting alternating red (660 nm) and infrared (810 nm) light, and the other couples to a photodetector (PD). (b) Dynamic change of \(F_{{\mathrm{i}}{{\mathrm{O}}_2}}\) (top) and corresponding \(S_{{\mathrm{t}}{{\mathrm{O}}_2}}\) results (bottom). (c) Dynamic response of \(S_{{\mathrm{t}}{{\mathrm{O}}_2}}\) collected in CA3 immediately after kindling. Top: Heatmap of 9 individual trials from n = 3 mice. Bottom: Average StO2 signals. The solid lines and shaded areas indicate the mean and s.e.m., respectively.
Extended Data Fig. 8 Representative confocal fluorescence images.
showing immunohistochemical staining for nuclei (DAPI, blue), astrocytes (GFAP, purple) and merged images after probe implantation for (a) 0, (b) 7 and (c) 28 days. Lesion areas are outlined by white dashed lines.
Extended Data Fig. 9 Representative confocal fluorescence images.
showing immunohistochemical staining for DAPI (blue), endothelial cells in blood vessels (CD31, green), immunoglobulin G (IgG, red) and merged images after probe implantation for (a) 0, (b) 7 and (c) 28 days. Lesion areas are outlined by white dashed lines.
Supplementary information
Supplementary Information
Supplementary Discussion, Figs. 1–16 and Tables 1–4.
Supplementary Video 1
Video of the behaviour of three mice implanted with O2-sensing probes and head-mounted circuits. Their \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) signals were recorded simultaneously.
Supplementary Video 2
Video (3× speed) showing the simultaneously recorded \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) signal in ipsilateral CA3 and the LFP signal in CA1, in a freely moving mouse, during AD induced by electrical stimulation at CA1.
Supplementary Video 3
Video (3× speed) showing the simultaneously recorded \(p_{{\mathrm{bt}}{{\mathrm{O}}_2}}\) signal in contralateral M1 and the LFP signal in CA1, in a freely moving mouse, during AD induced by electrical stimulation at CA1.
Source data
Source Data
Source data for Figs. 1–5 and Extended Data Figs. 1–9.
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Cai, X., Zhang, H., Wei, P. et al. A wireless optoelectronic probe to monitor oxygenation in deep brain tissue. Nat. Photon. 18, 492–500 (2024). https://doi.org/10.1038/s41566-023-01374-y
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DOI: https://doi.org/10.1038/s41566-023-01374-y
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