Research ArticleAPPLIED SCIENCES AND ENGINEERING

A swarm of slippery micropropellers penetrates the vitreous body of the eye

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Science Advances  02 Nov 2018:
Vol. 4, no. 11, eaat4388
DOI: 10.1126/sciadv.aat4388
  • Fig. 1 Schematic of the three-step targeted delivery procedure used for the slippery micropropellers.

    (1) Injection of the micropropellers into the vitreous humor of the eye. (2) Magnetically driven long-range propulsion of the micropropellers in the vitreous toward the retina. (3) Observation of the micropropellers at the target region near the surface of the retina by OCT.

  • Fig. 2 Fabrication and characterization of the perfluorocarbon-coated “slippery” micropropellers.

    (A) Schematic of the fabrication process. (B) SEM (top) and ESB-SEM (bottom) images of the micropropellers. The yellow arrows indicate the length (l) of the propeller and the diameter (d) of the head of the propeller. The white area is the nickel part of the propeller. Scale bars, 500 nm. (C) FTIR spectroscopy of the micropropellers without coating and with the perfluorocarbon coating, and the perfluorocarbon liquid. The enlarged spectra are displayed at the bottom right, proving the presence of the perfluorocarbon. The contact angles of the wafer with an array of coated helices (top) and uncoated helices (bottom) are shown, respectively.

  • Fig. 3 Controllable movement of the perfluorocarbon-coated micropropellers in the vitreous humor.

    (A) Schematic and time-lapse microscopy images showing the incomplete rotation of an uncoated micropropeller for one period (p) in the vitreous. (B) Schematic and time-lapse images showing the magnetically powered propulsion of the coated slippery propeller in the vitreous for 1.5 s (nine periods). In both schematic images, the green and the red dashed lines indicate the original position of the particles and the position of the particles during the application of the rotating magnetic field, respectively. The red arrows in both figures indicate the propulsion direction of the propeller. Scale bars, 1 μm. (C) Rotation angle of the uncoated propeller and the slippery propeller in the vitreous under the application of a rotating magnetic field. (D) Measured passive diffusion coefficients of uncoated silica particles and the slippery layer–functionalized particles in the vitreous. (E) Controllable magnetic field–driven propulsion of the coated micropropellers in the vitreous. The lines indicate the trajectories of the propellers (movie S4). Scale bar, 20 μm. (F) Dependence of the propulsion velocity of the slippery micropropellers on the driving frequency of the magnetic field in the vitreous, 25% glycerol solution, and water, respectively. Error bars represent SDs.

  • Fig. 4 Characterization of the movement the slippery micropropellers in the vitreous.

    (A) Two typical trajectories of the micropropellers and their corresponding dynamic velocities (inset). (B) Histograms of the dynamic velocities of the microhelices in the vitreous and 25% glycerol. (C) Flexural trajectories of the slippery micropropellers in the vitreous over a horizontal distance of 100 μm. (D) Directionalities between the start and end points over a horizontal distance of 100 μm. The distribution of the TA of the micropropellers in the vitreous is statistically analyzed (n > 60).

  • Fig. 5 Movement of the slippery micropropellers in the complete eyeball.

    (A) Schematic illustrating the movement of the slippery micropropellers in the vitreous (V) toward the retina (R). Passive fluorescent particles are injected with the micropropellers to mark the injection position. (B) Fluorescent microscopy image of the incised retina at the target region after the magnetic propulsion. Micropropellers [loaded with fluorescent nanodiamonds (red)] are observed on the retina [cell nuclei stained by DAPI (blue)]. Scale bar, 20 μm. (C) Fluorescence image shows that the passive fluorescent particles are located near the center of the vitreous. Scale bar, 1 mm. (D) Autofluorescence image of the retina near the optic disc. “D” stands for optic disc. Scale bar, 1 mm. (E) Colormap calculated by the three-dimensional (3D) reconstruction of the OCT scans, showing the distribution of the micropropellers in the corresponding dashed-line box in (D). (F and G) OCT images of X and Y scans, respectively, near the propellers’ landing zone. The dashed-line circles label the region of the micropropellers near the retina. The scan planes are indicated as green arrows in (D). (H) OCT image of the Y scan away from the optic disc, indicated as the yellow arrow in (D). Scale bars, 500 μm in (F to H).

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/4/11/eaat4388/DC1

    Fig. S1. Schematic of the experimental scheme used to confirm the movement of the propellers in the vitreous.

    Fig. S2. Intravitreal propulsion of micropropellers with different coatings.

    Fig. S3. SEM images of the micropropellers grown with TiO2 and Fe.

    Fig. S4. Time-lapse images showing the controlled movement (forward/backward) of the slippery Fe-containing propellers when actuated by the external magnetic field.

    Fig. S5. Percentage of propelling micropropellers containing Ni (black) and those made with Fe (red) in vitreous with different surface coatings.

    Fig. S6. Percentage of propelling slippery propellers in vitreous before and after incubation within 5% bovine serum albumin in PBS solution for 2 hours.

    Fig. S7. Characterization of the surface coating on the micropropellers by AFM.

    Fig. S8. Intravitreal propulsion of the slippery propellers as a function of the magnetic field strength.

    Fig. S9. Propulsion of the slippery micropropellers in glycerol solution.

    Fig. S10. Fluorescence images of the excised retina.

    Fig. S11. Investigation of the distribution of the propellers on the retina.

    Fig. S12. The M-H curve of a wafer piece (area of 10 mm2) containing an array of microhelices.

    Table S1. Statistical analysis of micropropellers moving in vitreous as a function of the surface coating.

    Movie S1. Wobbling motion of an uncoated micropropeller in the vitreous under the actuation of a rotating magnetic field with a strength of 8 mT and a frequency of 6 Hz.

    Movie S2. Propulsion of a slippery micropropeller in the vitreous under the actuation of a rotating magnetic field with a strength of 8 mT and a frequency of 6 Hz.

    Movie S3. A large swarm of slippery micropropellers moves across the boundary of an aqueous buffer into the vitreous and continues propelling in the vitreous under a rotating magnetic field with a strength of 8 mT and a frequency of 70 Hz.

    Movie S4. Controlled motion of slippery micropropellers in the vitreous under a rotating magnetic field with a strength of 8 mT and a frequency of 50 Hz.

    Movie S5. OCT shows the distribution of the slippery micropropellers at the vitreous-retina boundary.

  • Supplementary Materials

    The PDF file includes:

    • Fig. S1. Schematic of the experimental scheme used to confirm the movement of the propellers in the vitreous.
    • Fig. S2. Intravitreal propulsion of micropropellers with different coatings.
    • Fig. S3. SEM images of the micropropellers grown with TiO2 and Fe.
    • Fig. S4. Time-lapse images showing the controlled movement (forward/backward) of the slippery Fe-containing propellers when actuated by the external magnetic field.
    • Fig. S5. Percentage of propelling micropropellers containing Ni (black) and those made with Fe (red) in vitreous with different surface coatings.
    • Fig. S6. Percentage of propelling slippery propellers in vitreous before and after incubation within 5% bovine serum albumin in PBS solution for 2 hours.
    • Fig. S7. Characterization of the surface coating on the micropropellers by AFM.
    • Fig. S8. Intravitreal propulsion of the slippery propellers as a function of the magnetic field strength.
    • Fig. S9. Propulsion of the slippery micropropellers in glycerol solution.
    • Fig. S10. Fluorescence images of the excised retina.
    • Fig. S11. Investigation of the distribution of the propellers on the retina.
    • Fig. S12. The M-H curve of a wafer piece (area of 10 mm2) containing an array of microhelices.
    • Table S1. Statistical analysis of micropropellers moving in vitreous as a function of the surface coating.
    • Legends for movies S1 to S5

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    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.avi format). Wobbling motion of an uncoated micropropeller in the vitreous under the actuation of a rotating magnetic field with a strength of 8 mT and a frequency of 6 Hz.
    • Movie S2 (.avi format). Propulsion of a slippery micropropeller in the vitreous under the actuation of a rotating magnetic field with a strength of 8 mT and a frequency of 6 Hz.
    • Movie S3 (.avi format). A large swarm of slippery micropropellers moves across the boundary of an aqueous buffer into the vitreous and continues propelling in the vitreous under a rotating magnetic field with a strength of 8 mT and a frequency of 70 Hz.
    • Movie S4 (.avi format). Controlled motion of slippery micropropellers in the vitreous under a rotating magnetic field with a strength of 8 mT and a frequency of 50 Hz.
    • Movie S5 (.avi format). OCT shows the distribution of the slippery micropropellers at the vitreous-retina boundary.

    Files in this Data Supplement:

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