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, 28 (4), 571-582

Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature

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Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature

Sylvain Martel et al. Int J Rob Res.

Abstract

Although nanorobots may play critical roles for many applications in the human body such as targeting tumoral lesions for therapeutic purposes, miniaturization of the power source with an effective onboard controllable propulsion and steering system have prevented the implementation of such mobile robots. Here, we show that the flagellated nanomotors combined with the nanometer-sized magnetosomes of a single Magnetotactic Bacterium (MTB) can be used as an effective integrated propulsion and steering system for devices such as nanorobots designed for targeting locations only accessible through the smallest capillaries in humans while being visible for tracking and monitoring purposes using modern medical imaging modalities such as Magnetic Resonance Imaging (MRI). Through directional and magnetic field intensities, the displacement speeds, directions, and behaviors of swarms of these bacterial actuators can be controlled from an external computer.

Figures

Fig. 1
Fig. 1
Representation of the MC-1 MTB as a computer controllable bio-actuator with its flagella bundles (FB) for propulsion and its chain of magnetosomes (bottom) allowing steering control through magnetotaxis
Fig. 2
Fig. 2
Swimming speed distribution of the unloaded and non pre-selected MC-1 bacteria in an aqueous medium at room temperature.
Fig. 3
Fig. 3
Effect of the temperature on the swimming speed of unloaded MC-1 MTB in blood at 37°C
Fig. 4
Fig. 4
Various loading strategies; (a) Loading inside the cell; (b) Attaching nanoparticles to the cell; (c) MTB pushing or pulling an attached microparticles or micro-objects such as demonstrated in (Martel et al. 2006); and (d) Experiments conducted by our research group showing a swarm of MTB used to move a larger object not attached to the MTB all under computer feedback control as seen by sequence 1 to 3 under an optical microscope.
Fig. 5
Fig. 5
Swimming speeds of the MC-1 cells (velocity of 223μm/s when not subject to wall effect) for different microchannel widths. The graph shows that the velocity in channel widths similar to the narrower capillaries decrease much less than the theoretical model applied to non-biological objects. Although this needs further investigation, this may suggest a thrust force compensation of the MC-1 bacteria when swimming in such conditions.
Fig. 6
Fig. 6
Swimming speeds of the MC-1 bacteria versus the magnitudes of a Direct Current (DC) magnetic field. A: Bacteria have growth under anaerobic condition and only very small amounts of oxygen added daily. B: Bacteria have growth in medium containing 1% oxygen.
Fig. 7
Fig. 7
Magnetic field lines (Tesla) generated by a magnetosome chain superimposed on an electron microscopy image of the bacterium. In this simulation, we consider the presence of 11 magnetosomes with a mean diameter of 70nm. The distance between the magnetosomes is of 20nm. The saturation magnetization for magnetite (0.6T) is considered since at the MRI field of 1.5T, the magnetite chain is saturated.
Fig. 8
Fig. 8
(a) Simulation of the local magnetic field perturbation for a uniformly distributed concentration of MTB; The distance between MTB is 25μm corresponding to a concentration of approximately 107 cells/ml. (b) Turbo spin echo sequence imaging of several samples of MTB of different concentrations. From 1 to 8 the concentrations are 0, 0.19, 0.30, 0.51, 0.73, 0.84, 0.90, 1 ×108 cells/ml. These experimental data confirm the possibility of tracking the MTB using MRI. The sequence parameters are TR/TE = 5620/127ms, Echo Train Length (ETL) = 27, 512×408 pixels and a spatial resolution of 0.254mm. When the concentration of MTB increases, the transverse relaxation rate increases leading to a decrease of the signal intensity.
Fig. 9
Fig. 9
(a) A single MTB pushing a 3μm bead; (b) The same MTB pushing the bead and directed to turn left 30 degrees after 2.5 seconds, B1 and B2 indicate the direction of the magnetic field; (c) and (d) Swimming path of a swarm of MTB being controlled inside microfluidic channels.
Fig. 10
Fig. 10
Percentage of re-polarized (re-magnetized) MC-1 cells using a single one-second duration re-polarization pulse of different magnitudes
Fig. 11
Fig. 11
MC-1 bacterium versus propulsion/steering magnetic gradient coils for human showing the potential advantage of bacterial actuation for carriers or nanorobots navigating in smaller capillaries. The graph considers 50% Permendur (highest magnetization saturation material) per unit volume to leave room for embedding therapeutic agents.
Fig. 12
Fig. 12
Simplified schematics showing the various steps and vessel diameters used to reach the tumoral lesion.
Fig. 13
Fig. 13
Main hardware modules of the robotic platform for the MRI-trackable medical nanorobots

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