Research ArticleMEDICAL ROBOTS

Multifunctional biohybrid magnetite microrobots for imaging-guided therapy

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Science Robotics  22 Nov 2017:
Vol. 2, Issue 12, eaaq1155
DOI: 10.1126/scirobotics.aaq1155
  • Fig. 1 Dip-coating of S. platensis, C. reinhardtii, and T. subcordiformis.

    (A) Schematic of the dip-coating process of S. platensis in a suspension of Fe3O4 NPs. Bottom: MSP-6h/24h/72h represent the magnetized S. platensis subject to 6-/24-/72-hour dip-coating treatments, respectively. As the dipping time increased, the amount of Fe3O4 NPs, and hence thickness of the Fe3O4 coating on the S. platensis, also increased. (B) FESEM (top) and fluorescence images (bottom) of MSP-24h, MCR-24h, and MTS-24h samples. The fluorescence images were taken by a Leica SP8 confocal laser scanning microscope with excitation at 552 nm.

  • Fig. 2 Magnetic actuation of BMRs.

    (A) Schematics of the magnetic actuation for MSP, MCR, and MTS, wherein V represents the translational velocity, B denotes the strength of the magnetic field, f represents the input frequency of the magnetic field, ω indicates the rotation velocity of the microsphere, and θ denotes the tilt angle between the rotation axis of the microsphere and z axis. (B) Time-lapse image sequences of the controlled locomotion of MSP-72h, MCR-24h (θ = 90°), and MTS-24h, with time instants marked and motion trajectories delineated. The input magnetic field strength and frequency were 7.5 mT and 10 Hz for MSP-72h and 7.5 mT and 5 Hz for MCR-24h. For MTS-24h, the magnetic field used is shown in fig. S9. (C) Velocity-frequency profiles for three-pitch MSP-6h/24h/72h samples in water. (D) Swimming performances of three-pitch MSP-24h in diluted blood, gastric juice, and urine (all extracted from SD rats), respectively. (C) and (D) were obtained under a magnetic field strength of 7 mT in a range of rotation frequencies. The three-pitch body length for the MSP samples was obtained via sonication of the S. platensis before the dip-coating process. The error bars represent the standard deviation of three tests.

  • Fig. 3 Fluorescence properties of MSP.

    (A) Fluorescence emission spectra of MSP-0h, MSP-6h, MSP-24h, and MSP-72h (all 100 μg/ml) in DI water. (B) Fluorescence intensity of MSP-72h (100 μg/ml) versus illumination time at 660-nm emission. (C) Fluorescence emission spectra of MSP-72h (100 μg/ml) in solutions of different solvents and pH values. (D) Fluorescence intensity, (E) FWMH, and (F) wavelength of the emission peak for MSP-72h samples with varied concentration in solutions of different solvents and pH values. All fluorescent signals were recorded using a Hitachi F-7000 Fluorescence Spectrophotometer with an excitation wavelength of 552 nm.

  • Fig. 4 Fluorescence-based in vivo imaging of MSP.

    (A) Fluorescence of 100 μl of MSP-72h with varied concentrations in the subcutaneous tissue of nude Balb/c athymic mice at three residence times. The residence time is 0 min unless otherwise specified. Fluorescence of 300 μl of (B) MSP-72h, (C) MSP-24h, and (D) MSP-6h (all 800 μg/ml) in the intraperitoneal cavity at various residence times. Image sequences of (C) and (D) were recorded at the same time intervals with (B). The magnetic needle was placed at t = 3 min.

  • Fig. 5 T2-weighted cross-sectional MR imaging of MSP swarms inside SD rats.

    (A) MSP swarm of two different concentrations inside the subcutaneous tissues. (B) MSP swarm of two different concentrations inside the stomachs. (C) MSP swarm with the same concentration but subject to actuation and steering (with a rotating magnetic field) of different time periods before MR imaging across the rat’s stomach.

  • Fig. 6 Degradation of MSP samples in 37°C DPBS solution.

    (A) MSP-0h. (B) MSP-6h. (C) MSP-24h. (D) MSP-72h. In (A), the first three images are optical sequences showing the degradation process of MSP-0h, and the last image is a FESEM image with an enlarged view of one MSP-0h residue in the third optical image. (B) to (D) are organized likewise.

  • Fig. 7 Cytotoxicity of MSP samples to normal and cancer cell lines.

    (A) Normal cell line 3T3. (B) Cancer cell line SiHa. (C) Cancer cell line Hep G2. From left to right in each column are MTT assays for MSP-0h, MSP-24h, and MSP-72h. In all results, the zero-concentration group with 100% cell viability is set as the control. Six other concentration groups, that is, 25, 50, 100, 200, 400, and 800 μg/ml, are examined and compared with the control group. *P < 0.05 is considered as statistically significant. **P < 0.01, ***P < 0.001. The error bars represent the standard deviation of six independent experiments.

Supplementary Materials

  • robotics.sciencemag.org/cgi/content/full/2/12/eaaq1155/DC1

    Section S1. Autofluorescence of biological materials

    Section S2. Dip-coating S. platensis with Fe3O4 NPs

    Section S3. Magnetic actuation of BMRs

    Section S4. Fluorescence properties and in vivo imaging

    Section S5. MR imaging in vitro and in vivo

    Section S6. Degradation of MSPs

    Section S7. Cytotoxicity to SiHa and 3T3 cell lines

    Fig. S1. Autofluorescence of biological materials with various structures.

    Fig. S2. Characterizing the autofluorescence of S. platensis, pine pollen, and S. cerevisiae.

    Fig. S3. Photostability tests in DI water for S. platensis (100 μg/ml), S. cerevisiae (1 mg/ml), and C. salina (100 μg/ml).

    Fig. S4. Characterization of S. platensis (i.e., MSP-0h) and Fe3O4 NPs.

    Fig. S5. ζ potential of S. platensis and Fe3O4 NP suspension at different pH.

    Fig. S6. Characterization of the magnetized S. platensis.

    Fig. S7. Magnetic hysteresis loops of MSP-6h/24h/72h (300 K, via VSM).

    Fig. S8. FESEM images of MSP-72h that has undergone a 5-min sonication treatment.

    Fig. S9. The periodically varying magnetic field for the actuation of MTS-24h.

    Fig. S10. Strength of the magnetic field generated by the permanent magnet B versus the distance d to its rotation axis.

    Fig. S11. Photostability test of MSP-72h.

    Fig. S12. Supplementary data for fluorescence-based in vivo imaging.

    Fig. S13. T2-weighted MR imaging of MSP samples in vitro and in vivo.

    Fig. S14. Degradation of MSP in 37°C DPBS solution.

    Fig. S15. Supplementary data for cytotoxicity evaluation.

    Fig. S16. CLSM imaging for 3T3 and SiHa cells cocultured with MSP-24h samples (0, 100, and 400 μg/ml) for 24 and 48 hours.

    Table S1. Quantitative measurement of Fe contents in MSP-6h/24h/72h samples.

    Table S2. Main distribution of body length (in pitches) for MSP samples under different conditions.

    Table S3. Viscosity of various fluids for in vitro/in vivo swimming experiments.

    Table S4. Quantitative data of the emission peaks for MSP-0h/6h/24h/72h samples in Fig. 3A.

    Table S5. Quantitative data of the emission peaks for MSP-0h/24h/72h samples before and after degradation.

    Movie S1. Magnetic actuation of three-pitch MSP-72h in DI water using a rotating magnetic field (7.5 mT and 10 Hz).

    Movie S2. Magnetic actuation of MCR-24h (θ = 90°) in DI water using a rotating magnetic field (7.5 mT and 5 Hz).

    Movie S3. Magnetic actuation of MCR-24h (θ = 0°) in DI water using a rotating magnetic field (7.5 mT and 3 Hz).

    Movie S4. Magnetic actuation of MTS-24h in water using a periodically varying magnetic field described in fig. S9.

    Movie S5. Magnetic actuation of three-pitch MSP-24h in diluted blood using a rotating magnetic field (7 mT and 6 Hz).

    Movie S6. Magnetic actuation of three-pitch MSP-24h in gastric juice using a rotating magnetic field (7 mT and 8 Hz).

    Movie S7. Magnetic actuation of three-pitch MSP-24h in urine using a rotating magnetic field (7 mT and 4 Hz).

    Movie S8. In vitro magnetic actuation of a MSP-72h swarm in PO (first pressed).

    References (7779)

  • Supplementary Materials

    Supplementary Material for:

    Multifunctional biohybrid magnetite microrobots for imaging-guided therapy

    Xiaohui Yan, Qi Zhou, Melissa Vincent, Yan Deng, Jiangfan Yu, Jianbin Xu, Tiantian Xu, Tao Tang, Liming Bian, Yi-Xiang J. Wang, Kostas Kostarelos, Li Zhang*

    *Corresponding author. Email: lizhang{at}mae.cuhk.edu.hk

    Published 22 November 2017, Sci. Robot. 2, eaaq1155 (2017)
    DOI: 10.1126/scirobotics.aaq1155

    This PDF file includes:

    • Section S1. Autofluorescence of biological materials
    • Section S2. Dip-coating S. platensis with Fe3O4 NPs
    • Section S3. Magnetic actuation of BMRs
    • Section S4. Fluorescence properties and in vivo imaging
    • Section S5. MR imaging in vitro and in vivo
    • Section S6. Degradation of MSPs
    • Section S7. Cytotoxicity to SiHa and 3T3 cell lines
    • Fig. S1. Autofluorescence of biological materials with various structures.
    • Fig. S2. Characterizing the autofluorescence of S. platensis, pine pollen, and S. cerevisiae.
    • Fig. S3. Photostability tests in DI water for S. platensis (100 μg/ml), S. cerevisiae (1 mg/ml), and C. salina (100 μg/ml).
    • Fig. S4. Characterization of S. platensis (i.e., MSP-0h) and Fe3O4 NPs.
    • Fig. S5. ζ potential of S. platensis and Fe3O4 NP suspension at different pH.
    • Fig. S6. Characterization of the magnetized S. platensis.
    • Fig. S7. Magnetic hysteresis loops of MSP-6h/24h/72h (300 K, via VSM).
    • Fig. S8. FESEM images of MSP-72h that has undergone a 5-min sonication treatment.
    • Fig. S9. The periodically varying magnetic field for the actuation of MTS-24h.
    • Fig. S10. Strength of the magnetic field generated by the permanent magnet B versus the distance d to its rotation axis.
    • Fig. S11. Photostability test of MSP-72h.
    • Fig. S12. Supplementary data for fluorescence-based in vivo imaging.
    • Fig. S13. T2-weighted MR imaging of MSP samples in vitro and in vivo.
    • Fig. S14. Degradation of MSP in 37°C DPBS solution.
    • Fig. S15. Supplementary data for cytotoxicity evaluation.
    • Fig. S16. CLSM imaging for 3T3 and SiHa cells cocultured with MSP-24h samples (0, 100, and 400 μg/ml) for 24 and 48 hours.
    • Table S1. Quantitative measurement of Fe contents in MSP-6h/24h/72h samples.
    • Table S2. Main distribution of body length (in pitches) for MSP samples under different conditions.
    • Table S3. Viscosity of various fluids for in vitro/in vivo swimming experiments.
    • Table S4. Quantitative data of the emission peaks for MSP-0h/6h/24h/72h samples in Fig. 3A.
    • Table S5. Quantitative data of the emission peaks for MSP-0h/24h/72h samples before and after degradation.
    • References (7779)

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    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.avi format). Magnetic actuation of three-pitch MSP-72h in DI water using a rotating magnetic field (7.5 mT and 10 Hz).
    • Movie S2 (.avi format). Magnetic actuation of MCR-24h (θ = 90�) in DI water using a rotating magnetic field (7.5 mT and 5 Hz).
    • Movie S3 (.avi format). Magnetic actuation of MCR-24h (θ = 0�) in DI water using a rotating magnetic field (7.5 mT and 3 Hz).
    • Movie S4 (.avi format). Magnetic actuation of MTS-24h in water using a periodically varying magnetic field described in fig. S9.
    • Movie S5 (.avi format). Magnetic actuation of three-pitch MSP-24h in diluted blood using a rotating magnetic field (7 mT and 6 Hz).
    • Movie S6 (.avi format). Magnetic actuation of three-pitch MSP-24h in gastric juice using a rotating magnetic field (7 mT and 8 Hz).
    • Movie S7 (.avi format). Magnetic actuation of three-pitch MSP-24h in urine using a rotating magnetic field (7 mT and 4 Hz).
    • Movie S8 (.avi format). In vitro magnetic actuation of a MSP-72h swarm in PO (first pressed).

    Files in this Data Supplement:

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