MRI-based Medical Nanorobotic Platform for the Control of Magnetic Nanoparticles and Flagellated Bacteria for Target Interventions in Human Capillaries

Abstract

Medical nanorobotics exploits nanometer-scale components and phenomena with robotics to provide new medical diagnostic and interventional tools. Here, the architecture and main specifications of a novel medical interventional platform based on nanorobotics and nanomedicine, and suited to target regions inaccessible to catheterization, are described. The robotic platform uses magnetic resonance imaging (MRI) for feeding back information to a controller responsible for the real-time control and navigation along pre-planned paths in the blood vessels of untethered magnetic carriers, nanorobots, and/or magnetotactic bacteria (MTB) loaded with sensory or therapeutic agents acting like a wireless robotic arm, manipulator, or other extensions necessary to perform specific remote tasks. Unlike known magnetic targeting methods, the present platform allows us to reach locations deep in the human body while enhancing targeting efficacy using real-time navigational or trajectory control. We describe several versions of the platform upgraded through additional software and hardware modules allowing enhanced targeting efficacy and operations in very difficult locations such as tumoral lesions only accessible through complex microvasculature networks.

Keywords

nanorobots bacteria medical robotics MRI target chemotherapy blood vessels

Get full access to this article

View all access options for this article.

References

Alexiou, C. , Arnold, W. , Klein, R.J. , Parak, F.G. , Hulin, P. , Bergemann C. , Erhardt, W. , Wagenpfeil, S. and Lübbe, A.S. ( 2000). Locoregional cancer treatment with magnetic drug targeting . Cancer Research, 60: 6641-6648.

Alexiou, C. , Jurgons, R. , Schmid, R. , Hilpert, A. , Bergemann, C. , Parak, F. and Iro, H. ( 2005). In vitro and in vivo investigations of targeted chemotherapy with magnetics nanoparticles . Journal of Magnetic Materials , 293: 389-393.

Alexiou, C. , Diehl, D. , Henninger, P. , Iro, H. , Röckelein, R. , Schmidt, W. and Weber, H. ( 2006). A high gradient magnet for magnetic drug targeting . IEEE Transactions on Applied Superconductivity, 16(2): 1527-1530.

Behkam, B. and Sitti, M. ( 2007). Bacterial flagella-based propulsion and on/off motion control of microscale objects . Applied Physics Letters, 90: 023902-4.

Bell, D.J. , Leutenegger, S. Hammar, K.M. , Dong. L.X. , and Nelson, B.J. ( 2007). Flagella-like propulsion for microrobots using a nanocoil and a rotating electromagnetic field. Proceedings of the IEEE International Conference on Robotics and Automation (ICRA), pp. 1128-1133.

Bettmann, M.A. , Heeren, T. , Greenfield, A. and Goudey, C. ( 1997). Adverse events with radiographic contrast agents: Results of the SCVIR Contrast Agent Registry . Radiology, 203: 611-620.

Bey-Oueslati, R. and Martel, S. ( 2006). Micro heat pipe fabrication: high performance deposition platform for electronics . Proceedings of the 5th International Workshop on Microfactories (IWMF), Besançon , France.

Charm, S.E. and Kurland, G.S. ( 1974). Blood Flow and Microcirculation. Wiley, New York.

Chanu, A. , Felfoul, O. , Beaudoin, G. and Martel, S. ( 2008). Adapting the software of MRI for the real-time navigation of endovascular untethered ferromagnetic devices . Magnetic Resonance in Medicine.

10.

Driscoll et al. (1984).

11.

Ergeneman, O. , Dogangil, G. , Kummer, M.P. , Abbott, J.J. , Nazeeruddin, M.K. and Nelson, B.J. ( 2008). A agnetically controlled wireless optical oxygen sensor for intraocular measurements . IEEE Sensors Journal, 8(1): 29-37.

12.

Felfoul, O. , Mathieu, J.-B. , Beaudoin, G. and Martel, S. ( 2008). MR-tracking based on magnetic signature selective excitation . IEEE Transactions on Medical Imaging, 27(1): 28-35.

13.

Fidleris, V. and Whitmore, R.L. ( 1961). Experimental determination of the wall effect for spheres falling axially in cylinder vessels . British Journal of Applied Physics, 12: 490-494.

14.

Hatch, G.P. and Stelter, R.E. ( 2001). Magnetic design considerations for devices and particles used for biological high-gradient magnetic separation (HGMS) systems . Journal of Magnetism and Magnetic Materials, 225(1-2): 262 - 276.

15.

Honda, T. , Arai, K. and Ishiyama, K. ( 1999). Effect on micro machine shape on swimming properties of the spiral-type magnetic micro-machine . IEEE Transactions on Magnetics, 35: 3688-3690.

16.

Josephson, L. , Perez, J.M. and Weissleder, R. ( 2001). Magnetic nanosensors for the detection of oligonucleotide sequences . Angewandte Chemie International Edition, 40: 3204-3206.

17.

Li, W.H. , Fraser, S.E. and Meade, T.J. ( 1999). A calcium-sensitive magnetic resonance imaging contrast agent . Journal of the American Chemical Society, 121: 1413-1414.

18.

Li, W.H. , Parigi, G. , Fragai, M. , Luchinat, C. and Meade, T.J. ( 2002). Mechanistic studies of a calcium-dependent MRI contrast agent . Inorganic Chemistry, 41: 4018-4024.

19.

Louie, A.Y. , Huber, M.M. , Ahrens, E.T. , Rothbacher, U. , Moats, R. , Jacobs, R.E. , Fraser, S.E. and Meade, T.J. ( 2000). In vivo visualization of gene expression using magnetic resonance imaging . Nature Biotechnology 18: 321- 325.

20.

Lowe, M.P. , Parker, D. , Reany, O. , Aime, S. , Botta, M. , Castellano, G. , Gianalio, E. and Pagliarin, R. ( 2001). pHdependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation . Journal of the American Chemical Society , 123: 7601-7609.

21.

Mankiewicz, M. , Mohammadi M. and Martel, S. ( 2007). Motion tracking and analysis system for magnetotactic bacteria . Proceedings of the International Symposium on Optomechatronic Technologies (ISOT), Lausane, Switzerland.

22.

Martel, S. , Mathieu, J.-B. , Felfoul, O. , Macicior, H. , Beaudoin, G. , Soulez, G. and Yahia, L’H. ( 2004). Adapting MRI systems to propel and guide microdevices in the human blood circulatory system . Proceedings of the 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, San Francisco, CA, pp. 1044-1047.

23.

Martel, S. ( 2005). Method and system for controlling micro-objects or micro-particles . US Patent Application 11/145,007.

24.

Martel, S. ( 2006a). Controlled bacterial micro-actuation . Proceedings of the International Conference on Microtechnology in Medicine and Biology (MMB), Okinawa, Japan.

25.

Martel, S. ( 2006b). Targeted delivery of therapeutic agents with controlled bacterial carriers in the human blood vessels . 2nd ASM/IEEE EMBS Conference on Bio, Micro and Nanosystems, San Francisco, USA.

26.

Martel, S. , Tremblay, C. , Ngakeng, S. and Langlois, G. ( 2006). Controlled manipulation and actuation of micro-objects with magnetotactic bacteria . Applied Physics Letters, 89: 233804-6.

27.

Martel, S. ( 2007). Magnetic resonance propulsion, control, and tracking at 24 Hz of an untethered device in the carotid artery of a living animal: an important step in the development of medical micro- and nanorobots . Proceedings of the 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), Lyon, France.

28.

Martel, S. , Mathieu, J.-B. , Felfoul, O. , Chanu, A. , Aboussouan, É. , Tamaz, S. , Pouponneau, P. , Beaudoin, G. , Soulez, G. , Yahia, L’H. and Mankiewicz, M. ( 2007a). Automatic navigation of an untethered device in the artery of a living animal using a conventional clinical magnetic resonance imaging system . Applied Physics Letters, 90(11): 114105-7.

29.

Martel, S. , Mathieu, J.-B. , Felfoul, O. , Chanu, A. , Aboussouan, E. , Tamaz, S. , Pouponneau, P. , Yahia, L’H. , Beaudoin, G. , Soulez, G. and Mankiewicz, M. ( 2007b). Medical and technical protocol for automatic navigation of wireless devices in the carotid artery of a living swine using a standard clinical MRI system . 10th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2007) , Brisbane, Australia.

30.

Mathieu, J.-B. , Beaudoin, G. and Martel, S. ( 2006). Method of propulsion of a ferromagnetic core in the cardiovascular system through magnetic gradients generated by an MRI system . IEEE Transactions on Biomedical Engineering, 53(2): 292-299.

31.

Mathieu, J.-B. and Martel, S. ( 2007). In vivo validation of a propulsion method for untethered medical microrobots using a clinical magnetic resonance imaging system . Proceedings of the IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS), San Diego, CA.

32.

Meade, T.J. , Taylor, A.K. and Bull, S.R. ( 2003). New magnetic resonance contrast agents as biochemical reporters . Current Opinion in Neurobiology, 13: 597-602.

33.

Mykhaylyk, O. , Dudchenko, N. and Dudchenko, A. ( 2005). Doxorubicin magnetic conjugate targeting upon intravenous injection into mice: high gradient magnetic field inhibits the clearance of nanoparticles from the blood . Journal of Magnetism and Magnetic Materials, 293(1): 473- 482.

34.

Quirini, M. , Webster, R.J. , Mensiassi, A. and Dario, P. ( 2007). Design of a pill-sized 12-legged endoscopic capsule robot . Proceedings IEEE International Conference on Robotics and Automation (ICRA), pp. 1856-1862.

35.

Seldinger, S.I. ( 1953). Catheter replacement of the needle in percutaneous arteriography; a new technique . Acta Radiologica, 39: 368-376.

36.

Steager, E. , Kim, C.-B. , Patel, J. , Bith, S. , Naik, C. , Reber, L. and Kim, M.J. ( 2007). Control of microfabricated structures powered by flagellated bacteria using phototaxis . Applied Physics Letters, 90: 263901-3.

37.

Tamaz, S. , Chanu, A. , Mathieu, J.-B. , Gourdeau, R. and Martel, S. ( 2008). Real-time MRI-based control of a ferromagnetic core for endovascular navigation . IEEE Transactions on Biomedical Engineering (accepted).

38.

Whitmore, R.L. ( 1968). Rheology of the Circulation. Pergamon , New York.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB