fp7-ict-2007-2 nano-actuators and nano-sensors for medical ...€¦ · nanoma: nano-actuators and...
TRANSCRIPT
(1)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
1
FP7-ICT-2007-2
Nano-Actuators and Nano-sensOrs for Medical Applications
NANOMA
FP7-ICT-2007-2
Nano-Actuators and Nano-sensOrs for Medical Applications
NANOMA
Coordinator: Antoine FERREIRA
Université d’Orlé[email protected]
(2)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
NANOMA PartnersNANOMA Partners
• Partner 1 University of Orléans (Coord.) (UORL) - France• Partner 2 Zenon S.A. (Zenon) - Greece
• Partner 3 ETH Zurich (ETHZ) - Switzerland
• Partner 4 Universität Oldenburg (Amir) - Germany
• Partner 5 Biomedical Research Foundation (BRF) - Greece
• Partner 6 University of Cyprus (UCY) - Cyprus
• Partner 7 FemtoTools (FemtoTools) - Switzerland
• Partner 8 Hospital Oldenburg (HOld) - Germany
(3)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
NanoRobotics – Ultra-Local Drug DeliveryNanoRobotics – Ultra-Local Drug Delivery
(Opensource Handbook of Nanoscience and Nanotechnology)
Challenge 1
Challenge 2
Challenge 3
Improved imaging
Localized therapy
Killing the cancer cells
Molecular Imaging & Therapy
(4)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Present State-of-the-Art in Magnetic Targeting (Trapping)
Present State-of-the-Art in Magnetic Targeting (Trapping)
• Magnet is positioned to trap the magnetic particles in order to deliver therapeutic agents;
• No navigation hence particles must be delivered close to the target but still loosing a significant quantity of particles;
• Only for targets near the skin due to higher gradient field towards the magnet;
• No closed-loop control since the particles cannot be tracked (lack of imaging modality).
Magnetic Field
Body surface
(5)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Early cancer stage I
Microcaprule-based drug delivey
Magnetic microcapsule sterring using MRI ystem
NANOMA ConceptNANOMA Concept
1. Enhanced diagnostics using MRI,
2. In-Vivo propulsion and navigation,
3. Targeted drug delivery using functionalized nanovectors.
New approach for diagnosing and New approach for diagnosing and treating breast cancer :treating breast cancer :
Concept and Motivation: Concept and Motivation: NANOMA aims at developing drug delivery microrobotic systems (composed of nanoActuators and nanoSensors) for the propulsion and navigation of ferromagnetic microcapsules in the cardiovascular system through the induction on magnetic gradients.
(6)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
NANOMA ObjectivesNANOMA Objectives
Scientific and Technological Objectives: Scientific and Technological Objectives:
•• Design and modeling of nanorobotic capsules: Design and modeling of nanorobotic capsules: Energy approach based on multi-scaled and multi-physics modeling and interactive computational tools.
•• FunctionalizationFunctionalization--based targeting of biocarriersbased targeting of biocarriers : : Biodistribution-driven mechanisms using surface functionalization processes at the nanocapsule surface (f-CNT and f-NP).
•• MRI navigable biocarriers in blood vessels : MRI navigable biocarriers in blood vessels : The integration of ferromagnetic particles allows potential MR-tracking and automatic delivery of biocarriers through induced forces generated by magnetic gradients from an upgraded MRI system.
• InIn--vivo MRvivo MR--tracking drug delivery in mouse cancer models: tracking drug delivery in mouse cancer models: Efficiency of drug release at specific site (breast cancer cell and/or tumor) will be tested (proof-of-concept): Cell lines and In-vivo,
(7)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Multidisciplinary FieldMultidisciplinary Field
Beneficiaries: BRF, HOld
Beneficiaries: ETHZ, UCY, Amir, FemtoTools
Beneficiaries: ZENON, UORL
(8)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Virtual Environment
Biomotors
Structures
Bonding
Links
Virtual manipulation
DatabaseX-ray or NMR Molecular
docking
• carbon-carbon
• DNA-carbon
• biotin-avidin
• H-bonds
Connecting
•Multi-finger haptic rendering
• 3D visual rendering
Force feedback
Multiscale Models
Interactive Modeling
SimulationDataglove
3D Vision
VR Interfaces
• Steering forces• Temperature and pH variation
Haptics
Design MethodologyDesign Methodology
(9)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
3D Computer-Aided Design3D Computer-Aided Design
(a) PEG‐functionalized polymer nanoparticle , (b) PEG‐functionalized carbon nanotube with encapsulated magnetic material, (c) encapsulated drug delivery for drug release.
(10)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
29/06/200910
Example of Design and SimulationExample of Design and Simulation
Nanocapsule design
Peptides
Drug Encapsulation
Lipid bilayer was Lipid bilayer was composed of 256 CG composed of 256 CG
DMPC lipids DMPC lipids
• Doxorubicin
• Epirubicin
• Taxol,
• Cytoxan.
(11)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
FexOyFexOy
water
Fe3+/Fe2+Fe3+/Fe2+
NH4OHFe2+/Fe3+
1) Magnetic Functionalization, Stabilization and Targeting of Polymer-based Micellar Nanoparticles
2) Functionalization of Nanotube Capsules
(a) CNTs filled with Magnetic Nanowires
(b) Filling iron oxide/nickel nanoparticles into CNTs
(c) Decorating iron oxide/nickel nanoparticles onto CNTs
Magnetic Functionalization of NanocapsulesMagnetic Functionalization of Nanocapsules
Magnetic nanoparticles will be used for MRI magnetic field actuation / guiding / tracking of the CNT capsules.
(12)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
• Objectives• Shell engineering processes
for fabricating CNT capsules will be implemented. The functionalization (filling and decoration) of CNTs with magnetic particles, bio active peptides, and polymers will also be investigated.
As-grown CNTs
Electric BreakdownMechanical Destruction Ultrasonic/Acid-etching
Mechanical Destruction
Electric Breakdown
Mechanical Destruction
Baking after washing
Mechanical Destruction
Ultrasonic/Acid-etching
Ultrasonic/Acid-etching
Magnetic Functionalization of NanocapsulesMagnetic Functionalization of Nanocapsules
(13)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Biological Functionalization of NanocapsuleBiological Functionalization of Nanocapsule
• Description of Tasks:
1.Magnetic and bio-chemical nano-functionalization with linked colloidal magnetite nanoparticles and antibodies.2.Thermal-mechanical nano-functionalization with nanoheater linked rods and bilayers.
• Objectives:- Bio-chemical surface functionalization of nanocapsule for target recognition and binding.- Structure characterization of components and
testing of their actuation properties in magnetic steering.
(14)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
MRI-Based Tracking and Propulsion of CapsulesMRI-Based Tracking and Propulsion of Capsules
• Can implement the three essential components for real-time controlled navigation of untethered devices in the human vasculature:
– Propulsion• Using the three imaging
orthogonal coils of the MRI system and implementing additional software
– Tracking• Using the conventional hardware
and software of the MRI system
– Control• By implementing control
algorithms on the computer system of the MRI platform based on tracking information
(15)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Fundamental Theory of Magnetic Propulsion using MRI
Fundamental Theory of Magnetic Propulsion using MRI
Magnetic Resonance Propulsion (MRP)
Schematic of the clinical MRI and its typical configuration
The induced force (F) depends on the volume (V) of the ferromagnetic core, the magnetization saturation (M) of the material, the magnetic gradients applied with 3D directional control from the three orthogonal coils.
• Magnetic force scales down L3 while drag force decreases L at low Re
• Gradient coils in the MRI bore are limited,
• Hard to track if not sufficient number of particles together;
•Small blood vessels cannot imaged.
(16)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Timeline for tracking and propulsion used within the environment of the MRI platform for the closed-loop displacement along pre-planned paths in blood vessels.
Timeline for Tracking and PropulsionTimeline for Tracking and Propulsion
Martel et al. (2006), Applied Physics Let.
(17)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Tracking and NavigationTracking and Navigation
b c d
MRI diagnostics of breast cancer
Magnetic steering navigation ? Path planning of nanocapsules
Magnetic and Biologically functionalized CNT
a
(18)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
Demonstration ScenariiDemonstration Scenarii
• Recognition and Tracking of an Object• Propulsion along a preplanned path• No flow, no overly complicated structure
PHASE 1: HumanPHASE 1: Human--sized Phantomsized Phantom
PHASE 2: AnimalPHASE 2: Animal
The efficacy and cytotoxicity studies will be performed initially in cells in culture.
PHASE 3: Cell CulturePHASE 3: Cell Culture
• Injection• Tracking• Propulsion/Control
(19)NANOMA: Nano-Actuators and Nano-Sensors for Medical Applications
ContactsContacts
Co-ordinator : Prof. Antoine FERREIRAUniversity of OrléansInstitut PRISME
Email: [email protected]
http://nanoma.zenon.gr/