Charles Tremblay

Controlled manipulation and actuation of micro-objects with magnetotactic bacteria

Bacterial actuation and manipulation are demonstrated where Magnetospirillum gryphiswaldense magnetotactic bacteria (MTB) are used to push 3 μ m beads at an average velocity of 7.5 μ m s − 1 along preplanned paths by modifying the torque on a chain of magnetosomes in the bacterium with a directional magnetic field of at least 0.5 G generated from a small programmed electrical current. But measured average thrusts of 0.5 and 4 pN of the flagellar motor of a single Magnetospirillum gryphiswaldense and MC-1 MTB suggest that average velocities greater than 16 and 128 μ m s − 1 , respectively could be achieved.

Magnetic Resonance Navigation of a Bead Inside a Three-Bifurcation PMMA Phantom Using an Imaging Gradient Coil Insert

This paper reports the successful navigation of a 1-mm Chrome-Steel bead along three consecutive polymethyl methacrylate channels inside the bore of a 1.5-T magnetic resonance imaging (MRI) scanner. The bead traveled at a mean velocity of 14 cm·s -1. This was accomplished using an imaging gradient coil (IGC) insert located inside the MRI tube. While targeting one side of a bifurcation has been previously demonstrated using unidirectional gradient coils, this is the first time that magnetic resonance navigation (MRN) of a bead along consecutive channels is reported. Experimental results confirm that a clinical regular MRI can be used to propel a 1-mm device. In addition, when used at maximum power, IGC temperature rise becomes a serious issue that can ultimately damage the insert and limit the overall performance. Consequently, this paper aims to give some insight into coil temperature management for IGC-assisted procedures. A 33-min thermal stress test was carried out using 100% of the IGC power. Steady-state oscillation can be reached by interleaving propulsion periods with cooling periods, thus enabling longer propulsion procedures. Experimental data showed that the cooling time can be used for imaging purposes with no performance loss, thus enabling MRN-assisted procedures with multiplexed particle distribution assessment.

Fringe Field Navigation for Catheterization

To navigate smaller magnetic guidewires and catheters deeper through narrower blood vessels, a very large directional magnetic gradient field is required. As such, superconducting magnets such as the ones used in clinical MRI scanners are known to far exceed resistive coils or permanent magnets for generating such high field. But because superconducting magnets are not appropriate for switching or modulating fields such as for the generation of 3D directional gradient forces, a new approach capable of very high directional gradient forces from such superconducting magnets and referred to here as Fringe Field Navigation (FFN) is introduced. To provide such high directional gradients with a relatively high magnetic field strength in the interventional space, FFN uses the external field known as the fringe field of the MRI scanner. Since such large magnet capable of generating a much higher but constant field cannot practically be moved, superior directional gradients are achieved by robotically positioning and moving the patient outside and in proximity of the scanner accordingly. Preliminary results with a 1.5 T clinical scanner indicate the possibility to perform whole body FFN using 6-DOF gradients of 2000-4000mT/m which is much larger than the 300mT/m achievable with existing magnetic catheter navigation platforms.

In vivo demonstration of magnetic guidewire steerability in a MRI system with additional gradient coils.

PURPOSE To assess the ability to control the steering of a modified guidewire actuated by the magnetic force of a magnetic resonance imaging system with additional gradient coils for selective arterial catheterization in rabbits. METHODS Selective catheterizations of the right renal artery, left renal artery, superior mesenteric artery, and iliac artery were performed on two rabbits. A 3D magnetic force was applied onto a magnetic bead placed at the tip of a guidewire. The ability of the guidewire to advance in the aorta without entering the side branches when the magnetic force was not applied was also evaluated. Steering of the guidewire was combined with a dedicated tracking system and its position was registered on the 3D model of a magnetic resonance angiography (MRA). RESULTS The magnetic catheterization of the renal arteries was successful and showed reproducibility. Superior mesenteric artery and iliac artery showed that the catheterization was feasible. These two arteries were difficult to visualize on MRA, making catheterization and setting the direction of the force more difficult. There was no inadvertent catheterization of side vessels when the guidewire was advanced with magnetic steering despite the hook shape at the tip of the guidewire caused by the alignment of the bead anisotropy with the permanent magnetic field. CONCLUSIONS This first evaluation of selective catheterization of aortic branches with a magnetic guidewire provided a successful steering in the less angled side branches and this modified guidewire was advanced in the aorta without inadvertent selective catheterization when manipulated without magnetic actuation.

Temperature Response of a Magnetic Resonance Imaging Coil Insert for the Navigation of Theranostic Agents in Complex Vascular Networks

The purpose of this paper is to provide some practical insights regarding the use of a commercially available imaging coil as a magnetic resonance navigation (MRN) propulsion actuator. MRN relies on magnetic resonance imaging (MRI) technology to navigate magnetic therapeutic or imaging agents to a target location. When such a target is accessible only through complex vessel pathways, an imaging gradient coil (IGC) insert can be used to generate high slew rate gradient pulses. Although temperature rise might not be an issue for imaging routines, knowing precisely the temperature coil response is of primary importance for MRN-assisted interventions as it may limit propulsion performance and ultimately lead to system breakdown. This paper reports the impact of four parameters, namely, duty cycle, frequency, amplitude, and gradient direction on the temperature behavior of an IGC with external diameter suitable to fit inside the bore of a clinical MRI scanner and internal diameter appropriate for small animals. A minimum rise time of 300 μs was measured and magnetic gradients up to 325 mT·m-1 were generated. The insert can sustain burst-mode propulsion at maximum power for slightly less than 2 min before reaching its maximum admissible temperature. Temperature management is one of the future challenges in MRN research.

Robotic platform for real-time tracking of a single fast swimming bacterium

In this paper we present a hardware architecture with software implementation able to track free swimming single 2µm in diameter MC-1 bacterium. The computer vision system operates at up to 77 fps at full speed and up to 24 fps when recording full 512×512 pixels frame from coupled-charge device (CCD) array. Closed-loop control with lock-in tracking is achieved using the Otsu Segmentation Method (OSM) with a cubic spline model-based predictive algorithm. Using the system, speed distribution of MC-1 cells has been recorded showing a m ean speed of 200µm/s. Tracking is demonstrated over a range of a few millimeters during 30 sec.

Magnetic Fringe Field Navigation of a guidewire based on Thin Plate Spline modeling

Fringe Field Navigation (FFN), a method first introduced by our group, aims at providing a high directional pulling force on a magnetic object such as a magnetic tip of a guidewire or other instruments. In a clinical setting, the pulling force is typically produced by the strong fringe field generated by the superconducting magnet of a clinical Magnetic Resonance Imaging (MRI) scanner. Because it is impossible or practical to move such a bulky magnet, directional changes are performed by robotically moving the patient in the magnetic fringe field outside the scanner. To do so, a homogenous transformation for each point in a set of discrete points in the magnetic field space must first be done and used to determine the position of the robotic manipulator to enable the steering of a guidewire equipped with a magnetic tip towards the desired direction. We used the Thin Plate Spline (TPS) method to model the magnetic field and to estimate the direction of the magnetic field required to navigate the guidewire along a predetermined path. We also propose guidelines for the sampling of the magnetic field to produce a more accurate TPS function. To prove the concept, we applied FFN on a small experimental prototype using a small permanent magnet and a robotic manipulator to steer a guidewire inside a phantom. The preliminary results suggest that the same approach could be scaled up for clinical applications taking advantage of the much stronger magnetic field generated by the superconducting magnet of already available MRI scanners.

Improved three-dimensional remote aggregations of magnetotactic bacteria for tumor targeting

MC-1 Magnetotactic bacteria are being harnessed as medical nanorobots to deliver therapeutic agents to tumors. To do so, sequences of magnetic fields are being generated by a special platform to enable these bacteria to aggregate within the tumor. Although such aggregations within a 3D volume have been achieved by our group in the past, here we show an improved version enabling faster swarming within a predetermined volume while offering more flexibility for the developments of new aggregation sequences.

Exploiting the responses of magnetotactic bacteria robotic agents to enhance displacement control and swarm formation for drug delivery platforms

Magnetotactic bacteria MC-1 (MTB) synthesize a chain of magnetic nanoparticles called magnetosomes to navigate in deep-sea environments by orienting themselves in the direction of the Earth’s magnetic field. MTB’s inherent mobility and ability to be controlled by exposition to an external magnetic field has become of increasing interest for micromanipulation and drug transport applications. In the traditional control schemes, MTB were oriented by exposure to an external magnetic field causing them to align with the magnetic field lines. Directional changes were applied below a critical frequency and, as such, MTB were still able to swim along the generated magnetic field lines. The approach presented here proposes to apply to the MTB an oscillating magnetic field with a frequency beyond a critical limit to in order to exploit the time averaging magnetic field motion behavior of the bacteria cells. Results indicate that a time-multiplexed magnetic field made of various directional cycling fields can control the MTB more efficiently with less power, which is an advantage for future human-scale medical applications.

Indirect MPI-based detection of superparamagnetic nanoparticles transported by computer-controlled magneto-aerotactic bacteria

MC-1 strain magneto-aerotactic bacteria recently used in cancer therapy and labeled with superparamagnetic nanoparticles are localized by magnetic particle imaging (MPI) spectrometry. A 8.5 mT drive field oscillating at 150 kHz is generated in a solenoid coil and placed near two receiving coils connected in series in a gradiometric configuration. The magnetic behavior of superparamagnetic particles attached to the MC-1 bacteria using MC-1 antibodies allowed the indirect detection of the MC-1 bacteria. It is moreover validated that the drive field does not break the covalent bond between the MC-1 antibodies coating the superparamagnetic particles and the MC-1 bacteria. The results presented here demonstrate the usability of a MPI device to provide a real-time evaluation of the evolution of cancer treatment using MC-1 bacteria as delivery vectors.