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Synthetic and living micropropellers for convection-enhanced nanoparticle transport

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Science Advances  26 Apr 2019:
Vol. 5, no. 4, eaav4803
DOI: 10.1126/sciadv.aav4803
  • Fig. 1 Conceptual overview of magnetically controlled micropropellers for convection-enhanced NP transport.

    (A) Conceptual schematic depicting a single microrobot, the ABF, enhancing mass transport of NPs at the vessel-tissue interface (left), and swarms of MTB generating convective flow to improve mass transport (right). ECM, extracellular matrix. (B) Schematic of magnetofluidic platform for NP mass transport studies using magnetically induced convection. The microfluidic chip is placed between the objective lens of an inverted optical microscope and the electromagnets (left). A schematic depicts the chip, consisting of an upper channel filled with NPs (red) and a lower water channel (blue) that both border a collagen matrix (gray) along restricting trapezoidal posts made of PDMS. NPs can passively diffuse into the collagen matrix along their concentration gradient toward the water channel.

  • Fig. 2 ABF locally perturbs fluid flow.

    (A) Schematic of a 200-μm-wide microfluidic channel with suspended ABF (36 μm long, 10 μm in diameter) positioned at the channel center (x,y,z) = (0,0,0). The upper channel contains water, whereas the lower channel contains 200-nm fluorescent NPs. (B) Snapshot of ABF in a 200-μm-wide channel perturbing the tracked paths of the 200-nm fluorescent NPs indicating fluid flow. Scale bar (top), 10 μm. A numerical simulation of two-fluid flow with an ABF at the interface, with color indicating concentration distribution (red, 1 mol/m3; blue, 0 mol/m3) of molecular species (bottom). (C) Velocity profile at positions upstream and downstream of the ABF. For the control, at x = +3 mm, an unperturbed laminar profile with peak velocity of 50 μm/s was simulated. At both x = +50 μm (upstream) and x = −50 μm (downstream), an increase in peak velocities is predicted, with the peak shifted closer toward the channel wall for the upstream case. (D) Simulation results for the y velocity component uy (orthogonal to and out of the channel) at the same positions as (C). In the vicinity of the ABF, a push directed orthogonal to the flow direction toward the channel wall is predicted.

  • Fig. 3 ABF locally enhances NP transport.

    (A) Schematic of the microfluidic device (left) and conceptual sketch of experiment with numbered regions of interest, areas 1 to 5 (right). The ABF was controlled such that it maintained its position at the center of the channel (above area 3) by swimming upstream against the flow. (B) Simulated flux and simulated particle tracking in vicinity of the ABF. Left: Snapshot of the simulated concentration at three outlets upstream, downstream, and at the ABF. The bar graph in the middle quantifies the flux in the outlet areas for the five regions of interest in the vicinity of the ABF integrated over 1000 s (black) and for the same outlets in a control channel without ABF (white) based on Eulerian computational modeling. Right: A snapshot of an experiment showing the effect of the ABF on particle trajectories downstream (top) and a snapshot of such particle trajectories derived from Lagrangian computational modeling using the particle tracing interface in COMSOL Multiphysics. Although the effect of the ABF is captured as symmetric in fluid flow simulations based on Eulerian modeling, particle tracing simulation experiments indicate a slight asymmetry with stronger effects downstream of the ABF. (C) Bright-field image of an ABF in a microfluidic channel showing three outlets. (D) Fluorescence images at the beginning (top) and end (bottom) of an experiment, capturing the transport of 200-nm red fluorescent NPs into collagen. Scale bar, 50 μm. (E) Fold increase in fluorescence intensity of areas 2 to 5 compared to upstream control, area 1 (n = 9; *P < 0.05, Student’s t test; ratio of mean intensity change over areas 2 to 5 to area 1). In the presence of a rotating ABF (black bar), a 1.75-fold increase in fluorescence intensity was measured. (F) Overall increase in penetration depth Δd was quantified by measuring the distance at which fluorescence intensity fell to 1/e of its maximum value at the channel wall at the start and end of the experiment. The mean penetration depth of areas 2, 3, 4, and 5 exhibited a 1.73-fold increase relative to area 1 (n = 9; *P < 0.05, Student’s t test; ratio of mean penetration depth change over area 5 to 2 to area 1).

  • Fig. 4 Ferrohydrodynamic pumping with controlled swarms of MTB.

    (A) Transmission electron micrograph of M. magneticum strain AMB-1. Scale bar, 0.5 μm. The magnetosomes are clearly visible, here formed in two distinct strings of iron oxide crystals. (B) Control of AMB-1 under static magnetic fields (top) and magnetic fields rotating in-plane at 1 Hz. Scale bar (bottom), 5 μm. (C) Postprocessed images of tracked, cosuspended, nonmagnetic, fluorescent NPs used to observe flow fields generated by a swarm of MTB exposed to a 12-mT magnetic field rotating at 10 Hz in the y-z plane. Traces in green correspond to traveled trajectories over 12 frames (~1 s). Positions are computed using band-pass filter with 25-pixel diameter, followed by peak finding (top). Bacterial motion can be steered by changing the direction of the vector of the rotating magnetic field, because the MTB translate within the plane of rotation (bottom). For an RMF vector around the x axis, bacteria rotate along y, generating a flow that transports NPs along y. (D) Translational velocity is plotted versus applied rotational frequency at two different magnetic field strengths. Translational velocity increases with frequency initially, but at sufficiently high frequencies, it decreases because fluidic drag torque overcomes the magnetic torque to prevent them from keeping up with the rotation of the field. The maximum synchronized frequency, also corresponding to the maximum translational velocity, is referred to as the step-out frequency ωmax. When the magnetic field strength is increased, the step-out frequency increases, as observed.

  • Fig. 5 Swarms of bacteria enhance NP transport.

    (A) Overview of NP transport experiment with MTB (top). Because MTB were spatially distributed across the channel, a homogenous increase across all five regions of interest was observed, as shown in the fluorescence images at the start and end of an experiment (t = 120 min). Scale bar, 100 μm. The intensity data were summed over all five outlets for analysis. (B) Sum of fluorescence intensity increase in all five outlets over time for MTB-NP transport without RMF (−RMF) and with RMF (+RMF; 5 mT and 6 Hz). (C) The normalized increase in fluorescence intensity over 120 min, relative to the initial intensity at t = 0, was measured to be a 1.63-fold increase for +RMF compared to a 1.26-fold increase for −RMF (n = 3; *P < 0.05, Student’s t test). (D) The initial slope, in terms of fluorescence intensity increase per time (normalized to the start), was threefold higher for experiments without actuation (n = 3; *P < 0.05, Student’s t test, over 20 frames). au, arbitrary units. (E) Relative penetration depth also increased in the presence of RMF actuation (n = 3; **P < 0.05, Student’s t test). (F) Fluorescence intensity increase versus time for reinitiation of NP transport exceeding diffusive equilibrium. An RMF is applied after a delay of 60 min (shaded region). (G) The rate of change of fluorescence intensity increased slightly, although not significantly, within the first 10 min upon magnetic field initiation (n = 5; P > 0.05, Student’s t test) but then rose 2.3-fold compared to the rate of change of fluorescence intensity in the last 10 min without bacterial actuation (n = 5; *P < 0.05, Student’s t test). ns, not significant; RFU, relative fluorescence units.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/4/eaav4803/DC1

    Supplementary Text

    Fig. S1. ABF fabrication process.

    Fig. S2. Experimental results and simulations in 200-μm-wide channels.

    Fig. S3. ABF perturbs local fluid flow and increases total fluid velocity.

    Fig. S4. Effect of ABF and position control.

    Fig. S5. Intensity increase over time.

    Fig. S6. Plots of NP penetration depth increase over time influenced by ABF.

    Fig. S7. Effect of channel diameter.

    Fig. S8. Effect of ABF diameter.

    Fig. S9. Control of motile MTB with rotational fields in plane.

    Fig. S10. Density effect.

    Fig. S11. MTB promotes homogenous transport enhancement.

    Movie S1. Swimming of ABF through dense NP solution along S shape.

    Movie S2. Swimming of ABF in two-fluid flow device.

    Movie S3. Zoom of ABF swimming in two-fluid flow device.

    Movie S4. ABF in one-fluid flow device.

    Movie S5. Control of a single, motile MTB under static magnetic fields.

    Movie S6. Control of swarm MTB under RMFs in-plane and out-of-plane.

    Movie S7. Control of swarm MTB (red) mixed with nonmagnetic Escherichia coli (green) under RMFs.

    Movie S8. Tracking of swarms of NP transported by MTB induced fluid flow.

    Movie S9. Fluorescent NP guided by fluid flow coupling to rotating swarms of bacteria.

    Movie S10. Control of green fluorescently labeled MTB in microfluidic device.

    Reference (42)

  • Supplementary Materials

    The PDF file includes:

    • Supplementary Text
    • Fig. S1. ABF fabrication process.
    • Fig. S2. Experimental results and simulations in 200-μm-wide channels.
    • Fig. S3. ABF perturbs local fluid flow and increases total fluid velocity.
    • Fig. S4. Effect of ABF and position control.
    • Fig. S5. Intensity increase over time.
    • Fig. S6. Plots of NP penetration depth increase over time influenced by ABF.
    • Fig. S7. Effect of channel diameter.
    • Fig. S8. Effect of ABF diameter.
    • Fig. S9. Control of motile MTB with rotational fields in plane.
    • Fig. S10. Density effect.
    • Fig. S11. MTB promotes homogenous transport enhancement.
    • Legends for movies S1 to S10
    • Reference (42)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mov format). Swimming of ABF through dense NP solution along S shape.
    • Movie S2 (.mov format). Swimming of ABF in two-fluid flow device.
    • Movie S3 (.avi format). Zoom of ABF swimming in two-fluid flow device.
    • Movie S4 (.avi format). ABF in one-fluid flow device.
    • Movie S5 (.mov format). Control of a single, motile MTB under static magnetic fields.
    • Movie S6 (.avi format). Control of swarm MTB under RMFs in-plane and out-of-plane.
    • Movie S7 (.mp4 format). Control of swarm MTB (red) mixed with nonmagnetic Escherichia coli (green) under RMFs.
    • Movie S8 (.mov format). Tracking of swarms of NP transported by MTB induced fluid flow.
    • Movie S9 (.mov format). Fluorescent NP guided by fluid flow coupling to rotating swarms of bacteria.
    • Movie S10 (.mp4 format). Control of green fluorescently labeled MTB in microfluidic device.

    Files in this Data Supplement:

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