Smart Nano Surgeon
EE235 Final Project
May. 12th 2009
Infinite Plus One (I.P.O)
Jun-suk
Hong-ki
Jong-Sun
Motivation - Today’s climate
•
Many diseases are threatening human all over the world.
Especially, cancer, AIDS, tumor are extremely dangerous
•
Brand “new” diseases such as SARS, “mad-cow” disease,
and Swine Influenza (SI) are breaking out.
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Introduction: NANO in Bio-medicine
•
•
•
•
•
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Small volume of reagent samples, required for analysis.
Low power consumption, lasts longer on the same battery.
Less invasive, hence less painful.
Integration permits many systems built on a single chip.
Batch processing can lower costs significantly.
Existing nanotechnology can be used to make these devices.
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Market Analysis
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Nanotechnology Market
$14 billion in
2004
$30 billion
in 2005
Nanotechnology
$2.6 trillion
in 2014
Very fruitful
market area
Nano-enabled products have the price premium of 11%
Lux Research, Nanotechnology Report, 4th, 2006
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Health Care Nanotechnology Product Needs
50% increase annually!
Lux Research, Nanotechnology Report, 4th, 2006
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National Health Expenditures
$2.4 trillion in 2008
$4.2 trillion in 2017
Our target market:
about $100 billion size
Projected to reach $4.3
trillion by 2017 (19.5% of
GDP)
4.3 times the amount
spent on national defense
An outlook for the future
10~20 years ahead.
Health Affairs, 2008
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Market Increase of Nano robot & MEMS
15% increase annually!
Lux Research, Nanotechnology Report, 4th, 2006
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Competitor Analysis
Drug delivery:
Works well like tablets, but
limited target, operation
Human doctors:
Great, but have limitation
for major new disease
since they cannot go into
Human body
Competitors
Capsule Endoscope:
Great for taking pictures,
communication by RFID
but low quality, no control
Nano Bug:
Not realized yet,
too conceptual
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Basic Concept
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Blueprint of Nano Surgeon
10-20 years in the future…
What do we mean by a nanosurgeon? Imagine…


…a EMT/first responder better able to address medical
emergencies before arriving at the hospital with a simple
injection.
…a self-administered at-home first-aid kit capable of
“surgery.”

…persistent in vivo health monitoring.

…surgery/repair on the cellular and molecular scale.
or…
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40 years ago
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Now, and Future. Our Surgeon will
Mobility/Control
Biomotor
Magnetic movement
Catalytic pump
Action
Drug release
Cauterization
Ablation
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Targeting/Sensing
Antigen targeting
Navigation via
chemotaxis
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Applications of Nano Surgeon
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Targeting
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Targeting
[] Purpose

Gradient detection – navigation via chemotaxis

Target locking (site specificity) – Action trigger (drug
release), accumulation (selective ablation).
[] Sensing requirements

Very low detection limit.

Label-free detection.

High specificity, low NSB.

Consistent, reliable signal output.

Size! (nano)
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Targeting
[] Sensors + Nano

High field enhancement (optical)

Better mass sensitivity (cantilever)
∆z = L2/t2 ∆s

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‘bulk’ depletion/accumulation (nanowire)
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Targeting
[] Nanowire field-effect sensor

Surface chemistry to covalently link antibody receptors to
nanowire.
Influenza A single virus particle detection in dilute solution.
Patolsky F. et.al. PNAS 2004;101:14017-14022
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Targeting
[] Nanowire field-effect sensor

≈100 virus particles per μl (≈0.16 fM)

Consistent signal change (≈20 nS) and duration (≈20 s)

High sensitivity with decreased sensing area low NSB

Linear response
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Targeting
[] Nanowire field-effect sensor

Detection limit: down to 10 fM and below shown

Label-free!

High specificity, low NSB.

Consistent, reliable signal output.

Size: down to 2-3nm wires. 2µm sensors demonstrated.
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Detection Limit Comparison
[] FOM

th
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105
.. 2009
2008
RIU, pg-mm-2, cfu/mL, µM…
Method
Detection Limit
SPRI
~1 nM (protein)
Flow SPR
~54 fM (DNA)
CNT
~25 nM (H202)
Optofluidic
Ring
~10 pM (DNA)
TIRF
~0.5 pM (DNA)
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Targeting
[] Selective Functionalization
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Targeting
[] Selective Functionalization
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Targeting
[] Ligand-mediated hinge-bending
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Control
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Current Technology of moving/control
Switzerland, ETH, Dr. Nelson
Magnetic Helmholtz Robot
Japan, Dr. Sudo
Magnetic swimming Robot
Canada, Dr. Martel
MRI based nano robot
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Controlling
Nanoscale
Robots
Isarel, Dr. Solomon
Fluidic Control
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Principle of MRI
Previous use:
Limited to diagnostic
Hardware:
Commercial
MRI
machines can be used
to generate required
magnetic field.
Commercial 3T MRI (Phillips)
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Common Coil Design to Control in vivo Robot
The Helmholtz Coil Pair
www.oersted.com/helm
holtz_coils_1.shtml
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The Magnetic Field Created
by Helmholtz Coil Pair
The Maxwell Coil Pair and
Direction of Current Flow
http://hyperphysics.phyastr.gsu.edu/hbase/magnetic
/helmholtz.html
http://physics-
nmr.la.asu.edu/probes/hight
emp/Images/maxwellpair.jp
g
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Magnetic Gradient Field
Microrobot
movement
with changing magnetic
field
Microrobot movement with
changing magnetic field
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Video Clip
Nano Robotics Lab, Prof. M. Sitti, Carnegie Mellon University
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Action
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Action

For better treatment,
Drug delivery
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Drug release
We need ‘smart’ drug injection
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Smart Drug delivery
-Biocompatibiliy
-Control over size
-Reproducibility
Nanofabrication
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Smart Drug delivery
Nano-porous silicon-based particle

Biocompatible

Photolithography-based fabrication
1)
Nitride deposit
2)
Patterning
3)
Anodizing (pores)
4)
Electropolishing

porous silicon particle
Cohen et. al., Biomedical Microdevices 5:3, 253-259,2003
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Smart Drug delivery
Nano-porous silicon-based particle

Biocompatible

Photolithography-based fabrication
1)
Nitride deposit
2)
Patterning
3)
Anodizing (pores)
4)
Electropolishing

porous silicon particle

Recently 1.6µm

Not flat shape
Cohen et. al., Biomedical Microdevices 5:3, 253-259,2003
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Smart Drug release
Biophysical barriers
-Osmotic pressure
-Diffusion
How to
overcome?
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Smart Drug release

Penentration enhancer

Fenestration

Conjugate molecular track movement

Abraxane – breast cancer medicine

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50% improved dosages
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Option
MRI resolution enhancing nanoparticles
Gadolinium-based, iron oxide based superparamagnatic nanoparticles
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Issues, Future &
Conclusion
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Critical Issue: Power
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Critical Issue: Power-Biomolecular motor
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If power issue is solved,
Novineon, Germany
SINTEF, Norway
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Future Progress
[1] Immerging Technologies





Nanoscale High Efficient VCSELS: Use of laser for tissue burning
SOC Level Integration: Self-decision of Smart Nanosurgeon
Miniaturization of Devices: Limit of total device is 1 um
Complex Synchronized Control: Control team of several nano
surgeon devices
Self Sufficient Power Supply
[2] Additional Applications



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Smart Toothpaste: Nano robots to clean mouth overnight
Nano
Plastic
Surgeon:
Termination
of
fat
cells
or
shifting/alternation of bones will lead to precise plastic surgery
Health Monitoring System: Nano robots kept in living organ to
monitor status
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Business Plan
Technical
Area
1st Stage
2009
2010
2nd Stage
2011
2012
2013
3rd Stage
2014
2015
2016
2017
-Chemical Sensor Development (Macro  Micro)
Optimization
Sensing
Action
Control
Power
Compatibility
Test
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Optimization
(Micro)
- System design
- Sampling/Drug Delivery
Basic Methodology(Macro)
- MRI control
Advanced Methodology(Micro)
- MRI control
Power Source (Macro)
:Bio Battery
:Wireless power supply
Power Source (Micro)
:Bio Battery
:Wireless power supply
Animal Experiment
:Sensing/Actuation/Cure
:Compatibility
Human Experiment
:Sensing/Actuation/Cure
:Compatibility
Group I.P.O
Conclusion - S.W.O.T Analysis
Strength
Weakness
•Innovative medical method
•Experiments in vivo (human)
•No surgery
•Price
•Simple and comfortable
•Feasibility
•Precise control
Opportunity
Threat
•Conquer all existing diseases
•Developments of other medical
•Other medical applications
devices are also very fast
•Doctor
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We need money !!
Current Status

Early Market Stage: Need R&D funds
competence, aiming for the chasm stage
The chasm
to
build
core
The mainstream
market
The early
market
New
Technology
Conventional
Technology
Conventional
Process
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New
Technology
Nano Surgeon
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References
S. Park et al, 2005 IEEE/RSJ International Conference, 2005
N. Haas, et al, BME 200/300 Design U of Winconsin –Madison, 2008
J. B. Mathieu, G. Beaudoin, IEEE Transaction on Biomedical Eng. Vol 53, No2, 2006
Z. Li et al, Applied Physics A, Vol. 80, 2005
A.K. Singh et al, Biosensors & Bioelectronics, Vol. 14, 1999
R. Bogue, Industrial Robot: An International Journal, 2008
K. B. Yesin, Experimental Robotics, 2006
K. B. Yesin, MICCAI, 2005
M. Sitti et al, IEEE International conference on Robotics and Automation, 2008
K. Ishiyama et al, IEEE transactions on Magnetics, 1996
M. Sitti, Nature, 2009
M. Sitti et al, Applied Physics Letter, 2009
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References
Keehan, S., et al., Health Affairs Web Exclusive W146: 21 February 2008.
Patolsky, F., et al., Proc. Natl. Acad. Sci. USA, 2004, 101, 14017.
Patolsky, F., et al., Materials Today, 2005, 8 (4), 20-28.
Sundararajan, S., et al., Nano Lett., 2008, 8 (5), 1271-1276.
Yake, A., et al., Biomacromolecules, 2007, 8 (6), 1958-1965.
Ferrari et al., Nature Revies, Vol. 5, March 2005, 161-171
Grayson et al., Proceedings of the IEEE, Vol. 92, No. 1, January 2004
Green et al., Annals of Oncology 17, June 2006, 1263-1268
Serda et al., Biomaterials Vol. 30, 2009, 2440-2448
Harisinghani et al., the New England Journal of Medicine, Vol. 348, No. 25, June 2003
Santini et al., Nature, Vol. 397, January 1999
Cohen et al., Biomedical Microdevices, 5:3, 2003, 253-259
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Where do you want to invest your $$$?
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Where do you want to invest your $$$?
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