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NanoNano--Robotics in Medical Applications:Robotics in Medical Applications:From Science Fiction to RealityFrom Science Fiction to Reality
Constantinos Mavroidis, Ph.D., Professor
Bio Nanorobotics Laboratory
Department of Mechanical and Industrial Engineering
Northeastern University, Boston, Massachusetts
http://www.bionano.neu.edu
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Northeastern UniversityNortheastern University
George J. Kostas Nanomanufacturing Center
at Northeastern University
1. Entrepreneur, CorporateOutreach and Staff Area
2. Soft Lithography andWet Chemistry Lab
3. Lithography andCharacterization
4. Cleanroom Facility
Located in Boston MA
Created in 1898 14,000 Undergraduates
3,500 Graduate Students
90 PhD Programs Experiential Learning /
Cooperative Education
Leader inNanomanufacturing
Strong PhD Program inNanomedicine
Facilities at the Kostas NanomanufacturingCenter
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NanomedicineNanomedicine
Healthcare Applications of
Nanomedicine(Wagner et al., Nature Biotechnology, 2006)
Nanomedicine is the process ofdiagnosing, treating, and preventing diseaseand traumatic injury, of relieving pain, and ofpreserving and improving human health, usingmolecular tools and molecular knowledge ofthe human body.(Freitas, 2006)
Nanomedicine: Application ofnanotechnology in medicine.
Nanotechnology refers to the science andengineering activities at the level of atoms andmolecules. A nanometer is a billionth of ameter, that is, about 1/80,000 of the diameterof a human hair, or 10 times the diameter of ahydrogen atom.
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Market and Activity EvolutionMarket and Activity Evolution
Nanomedicine Patents and Publications (Wagner et al., Nature Biotechnology, 2006)
Nanomedicine Market:$6.8B in 2004; $12B in 2012(Wagner et al., Nature Biotechnology, 2006)
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CollaborationCollaborationA truly multidisciplinary fieldA truly multidisciplinary field
Nanomedicine
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Role of Nanotechnology in Medical ResearchRole of Nanotechnology in Medical Research
Basic Research
Molecular Biology
Genetics
Proteomics
Systems Biology
.
Nanotechnology
Nanomanufacturing
Nanoimaging
Nanosensing
Nanomanipulation
Computational Tools
.
Biomedical Devices
Tissue Regeneration
Drug Delivery
In-vitro Diagnostics
Implantable Devices
Smart Nanoparticles
NanoRobotics
.
Translational ResearchCancer
Heart
Brain
.
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The NanoRobotic Concept
Nanorobots would constitute any smart structurecapable ofactuation, sensing, signaling, information
processing, intelligence, manipulation and swarmbehaviorat nano scale (10-9m).
Bio nanorobots Nanorobots designed (and inspired) byharnessing properties of biological materials (peptides,
DNAs), their designs and functionalities. These areinspired not only by nature but machines too.
Nanorobots could propose solutions at most of thenanomedicine problems
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NanoRobotics An Example:Ultra-Local Drug Delivery
Bio-Nano-Robot Repairing a Damaged Blood Cell
(Opensource Handbook of Nanoscience and Nanotechnology)
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Bio Sensors
DNA Joints
HA a-helix
A bio nano robot
Representative Assembly
of bio components
Assembled bio
nanorobots
Bio nano
components
A bio nanocomputational cell
Bio nano swarms
Distributive
intelligence
programming &
control
A Bio nano information
processing component
Conceptual automatic
fabrication floor
Automatic
fabrication and
information
processing
The Roadmap Towards NanoRobotics
STEP 1 STEP 2 STEP 3 STEP 4
Research Progression
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Bottom Up Approach Based on
Macro-Nano EquivalenceStructural Elements
Metal, Plastic Polymer DNA, Nanotubes
Actuators
Electric Motors,
Pneumatic Actuators,
Smart Materials, Batteries,
etc.
ATPase, VPL Motor, DNA, CNT
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Bottom Up Approach Based on
Macro-Nano EquivalenceSensors
Light sensors, force sensors,position sensors, temperature
sensors
Joints
Revolute, Prismatic,
Spherical Joints etc.
DNA
Nanodevices,
Nanojoints
Rhodopsin,
Heat Shock
Factor,
CNT based
Nanosensors
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State of the Art on NanoRobotics:Nanomanipulators
NanoRobotics for Molecular Biology
Cell Manipulation Using Nanomanipulators(e.g. automated DNA injection - Prof. Brad Nelsons group at ETH)
Commercial Nanomanipulators (e.g. Zyvex Corp.)
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State of the Art on NanoRobotics:MRI Guided Nanoparticle
In vivo automatic navigation of a 1.5 mm ferromagnetic bead inside thecarotid artery of a living swine (Martel et al., 2007, Applied Physics Letters).
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State of the Art on NanoRobotics:Smart Nanoparticles
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State of the Art on NanoRobotics:
Protein Based Nano Motors and SensorsProtein Based Molecular MachinesProtein Based Molecular Machines ATPATP SynthaseSynthase Motors,Motors, MyosinsMyosins,, KinesinsKinesins andand DyneinsDyneins, Bacterial Flagella, Bacterial Flagella
MotorsMotors
Advantages: Natural, High Efficiency and PowerAdvantages: Natural, High Efficiency and Power
Disadvantages: Bulky, Hard to Interface, Customize and Design, CDisadvantages: Bulky, Hard to Interface, Customize and Design, Complexomplex
Flagella in Bacterial MembraneATP Synthase ATPase Visualization1
Myosin Kinesin
Dynein MoleculeSteffen et al., Biol. Bulletin. 193, 221-222
1Noji et al., Nature, 386:(6622), 299-302
1 m diameter glass bead
carried by Kinesins
12/57
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Transcription Factor in Yeast, GCN4, Leucine Zipper
Peptide basedPeptide based NanoNano--GripperGripper
Collaborator: Prof. Martin Yarmush, Center of Engineering in Medicine, MGH - Harvard
The tweezer mechanism should be reversible
Introduce amino acids with different degree of ionization at varying pH
Specifically histidines can be incorporated at eand g positions
Ionized amino acids will generate repulsive electrostatic charges andmake the helices move away
The hydrophobic interactions should bring the helices back once the pHis increased
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Peptide basedPeptide based NanoNano--Gripper:Gripper:Potential ApplicationsPotential ApplicationsMetal-ion Sensor
Schematic of a MolecularTweezer based bio-sensor for metallic ions.
The nanoTweezer bindsthe metallic ions atneutral pH and canrelease them at low pH.
Molecular Switch
Schematic of a MolecularTweezer based molecular switchor a pH sensor which relies onthe change in conformation atlow pH. (a) At pH 7 the peptide
is in compact configuration andthe ions have access to the goldsubstrate; (b) At low pH thepeptide is in open configurationand the access of the ions isblocked by the passivatingdodecanethiol layers resulting inreduced conductivity.
low pH
Dodecanethiollayers
thiotic acidlinker
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Peptide basedPeptide based NanoNano--Gripper:Gripper:
ArchitecturesArchitectures
Wild-type Mutant M1 Mutant M2 Mutant M3 Control M3CT
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Peptide basedPeptide based NanoNano--Gripper:Gripper:
ResultsResults
pH = 4.0
pH = 7.0
A
pH = 4.0
pH = 7.0
B
-20 0 20
pH = 4.0
pH = 7.0
C
Frequency (MHz)0 2 4 6
pH = 4.0
pH = 7.0
Distance (nm)
D
k =0.2 k =0.4k =0.2 k =0.4
Displacement Calculation Using MD Simulations
Force Calculations Using MD Simulations
Experimental Verification Using ESR Spectrocopy
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Viral Protein Nano Motor
Influenza hemagglutinin (HA) is aviral surface protein.
Upon interaction with a cell surfacereceptor, it is endocytosed.
In the endosome, the pH drops to5.0 and the HA protein undergoes a
dramatic conformational change topromote fusion.
The lower pH of 5.0 allows theprotein to cross an energy barrierand refold into a more stable
conformation. Computational and experimental
study showed the validity of theconcepts and its dependence ontemperature and salt concentration.
Collaborator: Prof. Martin Yarmush, Center of Engineering in Medicine, MGH - Harvard
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NanoActuators and NanoSensors for
Medical Applications - NANOMA
Early cancer stage I
Microcaprule-based drug delivey
Magnetic microcapsule sterring using
MRI ystem
1. Enhanced diagnostics usingMRI,
2. In-Vivo propulsion and
navigation,
3. Targeted drug del ivery using
functionalized nanovectors.
New approach for diagnosing and
treating breast cancer :
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.
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Nanorobots for the Oil Industry
TRANSCEIVER ON BORE HOLE;
HARDWIRED TO THE DATA
CENTERNANOBOT
WIRELESS POWER &
DATA TRANSFER
DATA CENTER
OIL
RESERVOIR
BOREHOLE
Develop novel nanobots for the monitoring of deep oil reservoirs
Chemical Sensor
Pressure Sensor
Temperature Sensor
Power Source
Data Storage
Wireless
Communication
Magnetic Plates
Fish Tale Propulsion
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Future Challenges for Nanorobotics
Chemical Sensor
Pressure Sensor
Temperature Sensor
Power Source
Data Storage
Wireless
Communication
Magnetic Plates
Fish Tale Propulsion Assembly of a Fully FunctionalNanorobot
Closed Loop Control and Guidance atthe Nano-Scale
Wirelless Communication at the Nano-Scale Data Transfer
Power Generation at the Nanoscale
Accurate Modeling at the Nanoscale
Going Smaller and Smaller (~100nmtotal)
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Senior Investigator Team
Dr. M. Yarmush
Professor, Center ofEngineering in Medicine,MGH / Harvard Medical School
Dr. Yung-Joon Jung
Assistant Professor, Nanomanufacturing
Mechanical Engineering, Northeastern University
Dr. Antoine Ferreira
ProfessorModeling and ControlUniversity of Orleans, France
Dr. C. Mavroidis
Professor, RoboticsMechanical Engineering,Northeastern University
Dr. Marianna Bei
Assistant Professor
Molecular GeneticsMGH / Harvard Medical School
Dr. David Budil
Associate ProfessorChemistry and Chemical Biology
Northeastern University
Engineering Biomedical
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Acknowledgments
NASA Institute of Advanced Concepts(NIAC) Phase II Grant
NSF Nanomanufacturing Program NIRT Grant