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Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves

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Science Advances  05 Jul 2019:
Vol. 5, no. 7, eaaw5296
DOI: 10.1126/sciadv.aaw5296
  • Fig. 1 Wireless, battery-free neural cuff for programmable pharmacology and optogenetics.

    (A and B) Demonstrations of the overall size of the system. Scale bars, 5 mm. (C and D) Magnified views of the neural cuff interface with optical μ-ILED activation and fluid delivery. Scale bars, 1 mm. Exploded view (E) and electrical schematic diagram (F) of the wireless optofluidic system for programmable pharmacology and optogenetics. μC, microcontroller.

  • Fig. 2 Fluidic and electrical characteristics of the wireless optofluidic system.

    (A and B) Top: Schematic diagram of the electrochemical micropump. Applying current to a pair of electrodes initiates pumping through expansion induced by electrochemical phase change of liquid water into hydrogen and oxygen gases. The resulting pressure in the micropump chamber deforms the flexible membrane and delivers the drug. Bottom: Images of mechanical deformation of the flexible membrane induced by water electrolysis. Scale bar, 0.3 mm. (C) Fluid volume in the drug reservoir as a function of time. (D) Comparison between experiment and modeling of maximum displacement of flexible membrane induced by water electrolysis. (E) Current-voltage-power characteristics of the electrochemical micropump. (F) Total infusion efficiency from various loaded volumes in representative devices (n = 3 devices). (G) Flow rate in a microfluidic channel as a function of time. (H) Temperature of the drug chamber (top) and micropump chamber (bottom) during the electrochemical pumping process (3 V). All data are represented as means ± SEM.

  • Fig. 3 Implantation of the battery-free optofluidic nerve cuff system and its impact on animal behavior and nerve health.

    (A) Detailed illustration of the optofluidic nerve cuff system and cuff interface with the mouse sciatic nerve. (B) Demonstration of both optical stimulation and fluid delivery to the sciatic nerve. Scale bar, 2 mm. (C) Mouse chronically implanted with the wirelessly powered optofluidic nerve cuff system. (D) Characterization of effects of device implantation on rotarod performance compared to PE cuff and sham surgery [n = 9 to 10; ***P < 0.001 PE cuff versus sham and device, two-way analysis of variance (ANOVA)]. Mouse gait parameters including maximum contact mean intensity (E), swing time (F), and print area (G) are significantly impaired after PE cuff implantation but not after optofluidic cuff implantation compared to sham surgery (n = 8 to 10; ***P < 0.001, **P < 0.01, and *P < 0.05, one-way ANOVA with Tukey’s multiple comparison). Representative hematoxylin and eosin images (H) and quantification of infiltrating immune cells (I) from the sciatic nerve comparing sham, device, and PE cuff after 2 weeks (w) of implantation demonstrating an absence of infiltrating immune cells in sciatic nerves of mice implanted with the device compared to PE cuff implantation. Scale bars, 25 μm. n = 3; ***P < 0.001, one-way ANOVA with Tukey’s multiple comparison. AU, arbitrary units.

  • Fig. 4 Demonstration of optogenetic and microfluidic capabilities of the wireless, battery-free optofluidic nerve cuff system.

    (A) Schematic of the real-time place preference assay designed to test the capabilities of nerve cuff optical stimulation. Representative heat maps (B) and quantification (C) of blue light stimulation of sciatic nerve in wild-type and TRPV1-ChR2 mice. Mice were placed in the chamber for a total of 20 min. TRPV1-ChR2 mice displayed significant aversion to 1-Hz light pulse stimulus compared to wild-type mice (n = 9 to 10; *P < 0.05, two-way ANOVA with Sidak’s multiple comparisons test). (D) Optofluidic cuff devices loaded with bupivacaine and saline were implanted in mice, and thermal sensitivity was assayed before and after saline and again after bupivacaine infusion. (E) Quantification of the withdrawal latency to thermal stimulation of the ipsilateral (device side) and contralateral paw at baseline, after saline and after bupivacaine (n = 5 to 6; *P < 0.05 and **P < 0.01, one-way ANOVA with Sidak’s multiple comparisons test).

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/7/eaaw5296/DC1

    Note S1. Pressure in the pump chamber and drug reservoir.

    Note S2. Models for the radius of the cuff.

    Note S3. Analytical model of contact pressure between the nerve and the cuff.

    Note S4. Oxygen and hydrogen permeability of the flexible SBS membrane.

    Note S5. Mechanical characterizations of optofluidic probe.

    Note S6. Flow rate measurement.

    Fig. S1. Images of the wireless electronics and the complete system.

    Fig. S2. Detailed images of the electrochemical micropump.

    Fig. S3. Modulus and water permeability of the flexible SBS membrane.

    Fig. S4. Computational results for pressure in the pump chamber and the drug reservoir as a function of volume of drug delivered from the system.

    Fig. S5. Demonstration of drug loading and device reuse.

    Fig. S6. Mechanical properties of the soft opotofluidic probe.

    Fig. S7. Measurements of nerve temperature during various μ-ILED illumination protocols.

    Fig. S8. Diagrams of formation of cuff from bilayer PDMS strips.

    Fig. S9. Mechanical characterizations of cuff.

    Fig. S10. Demonstration of the dye delivery via the optofluidic cuff 2 weeks after implantation and the positive control PE tubing cuff implantation.

    Fig. S11. Schematic illustrations of the metal membrane on the PI substrate.

    Fig. S12. Schematic illustrations of the assembly of device.

    Fig. S13. Isochoric gas permeation system.

    Table S1. Oxygen and hydrogen permeability of the flexible SBS membrane.

    Table S2. Fabrication process details.

    Table S3. Statistical results for Fig. 3.

    Table S4. Statistical results for Fig. 4.

    Movie S1. The deformation of the flexible membrane.

    Movie S2. The flow of fluid from the reservoir.

    Movie S3. Mouse with a blue μ-LED during exercise on a running wheel.

    Reference (47)

  • Supplementary Materials

    The PDF file includes:

    • Note S1. Pressure in the pump chamber and drug reservoir.
    • Note S2. Models for the radius of the cuff.
    • Note S3. Analytical model of contact pressure between the nerve and the cuff.
    • Note S4. Oxygen and hydrogen permeability of the flexible SBS membrane.
    • Note S5. Mechanical characterizations of optofluidic probe.
    • Note S6. Flow rate measurement.
    • Fig. S1. Images of the wireless electronics and the complete system.
    • Fig. S2. Detailed images of the electrochemical micropump.
    • Fig. S3. Modulus and water permeability of the flexible SBS membrane.
    • Fig. S4. Computational results for pressure in the pump chamber and the drug reservoir as a function of volume of drug delivered from the system.
    • Fig. S5. Demonstration of drug loading and device reuse.
    • Fig. S6. Mechanical properties of the soft opotofluidic probe.
    • Fig. S7. Measurements of nerve temperature during various μ-ILED illumination protocols.
    • Fig. S8. Diagrams of formation of cuff from bilayer PDMS strips.
    • Fig. S9. Mechanical characterizations of cuff.
    • Fig. S10. Demonstration of the dye delivery via the optofluidic cuff 2 weeks after implantation and the positive control PE tubing cuff implantation.
    • Fig. S11. Schematic illustrations of the metal membrane on the PI substrate.
    • Fig. S12. Schematic illustrations of the assembly of device.
    • Fig. S13. Isochoric gas permeation system.
    • Table S1. Oxygen and hydrogen permeability of the flexible SBS membrane.
    • Table S2. Fabrication process details.
    • Table S3. Statistical results for Fig. 3.
    • Table S4. Statistical results for Fig. 4.
    • Reference (47)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mp4 format). The deformation of the flexible membrane.
    • Movie S2 (.mp4 format). The flow of fluid from the reservoir.
    • Movie S3 (.mp4 format). Mouse with a blue μ-LED during exercise on a running wheel.

    Files in this Data Supplement:

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