M' Meyyappan

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Nanotechnology Pharmaceutical and Biomedical
Applications
M. Meyyappan NASA Ames Research Center Moffett
Field, CA 94035 mmeyyappan_at_mail.arc.nasa.gov
Acknowledgement Jun Li
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What is Nanotechnology?
Source K.J. Klabunde, 2001
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Impact of Nanotechnology
Computing and Data Storage Materials and
Manufacturing Health and Medicine Energy
Environment Transportation National
Security Space exploration
Nanotechnology is an enabling technology
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Health and Medicine
New formulations and routes for drug
delivery, optimal drug usage More durable,
rejection-resistant artificial tissues and
organs, implantable electrodes Sensors for
early detection and prevention
Expanding ability to characterize genetic
makeup will revolutionize the specificity of
diagnostics and therapeutics - Nanodevices can
make gene sequencing more efficient Effecti
ve and less expensive health care using remote
and in-vivo devices
Nanotube-based biosensor for cancer diagnostics
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Nanomaterials in Drug Delivery
Dissolution kinetics may be the rate limiting
step in the absorption process for many
drugs - Decreasing the particle size increases
surface area and the dissolution
kinetics. Liposomes are normally used as
carrier for hydrophilic drugs. Typical
difficulties physical instability, low
activity, drug leakage - Alternative
water-soluble polymer based nanoparticles. These
are more site-specific and exhibit better
controlled-release characteristics. - To
overcome toxicity issues, solid lipid nanospheres
as carrier systems have been reported. This
is a lipid that is solidified and stabilized by
a surfactant. Advantages physical
stability Disadvantage low drug loading (25)
S.A. Wissing et al., Adv. Drug. Del. Rev. 56,
p. 1257 (2004).
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Dendrimers What are They?
Tree-like polymers, branching out from a
central core and subdividing into hierarchical
branching units - Not more that 15 nm in
size, Mol. Wt very high - Very dense surface
surrounding a relatively hollow core (vs. the
linear structure in traditional
polymers) Dendrimers consist of series of
chemical shells built on a small core
molecule - Surface may consist of acids or
amines ? means to attach functional groups ?
control/modify properties - Each shell is
called a generation (G0, G1, G2.) - Branch
density increases with each generation - Contain
s cavities and channels ? can be used to trap
guest molecules for various applications.
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Applications for Dendrimers Biomedical/Pharmaceut
ical
Desired features of effective drug
delivery - Targeted delivery, controlled
release (either timed or in response to an
external signal) Desirable
characteristics of dendrimers - Uniform
size - Water Solubility - Modifiable
surface functionality - Availability of internal
cavity - Control of molecular
weight - Control of the surface and internal
structure Number of different drugs can be
encapsulated in dendrimers and injected into the
body for delivery - Incorporating sensors
would allow release of drugs where needed Gene
Therapy - Current problem is getting enough
genes into enough cells to make a difference.
Using viruses for this triggers immune
reactions. Dendrimers provide an
alternative without triggering immune
response Cancer Therapy Antimicrobial and
Antiviral Agents
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Health and Medicine
New formulations and routes for drug delivery,
optimal drug usage More durable,
rejection-resistant artificial tissues and
organs, implantable electrodes Sensors for
early detection and prevention
Expanding ability to characterize genetic
makeup will revolutionize the specificity of
diagnostics and therapeutics - Nanodevices can
make gene sequencing more efficient Effecti
ve and less expensive health care using remote
and in-vivo devices
Nanotube-based biosensor for cancer diagnostics
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Current Techniques for Deep Brain Stimulation

• WHY Effective Clinical Technique
• DBS has been clinically effective in the
  treatment of movement disorder
• HOW Four Interrelated Hypothesis
• Paradox of similar effects to lesioning of
  target structure is explained by the following
• Depolarization Blockage
• Synaptic Inhibition
• Synaptic Depression
• Stimulation Induced Modulation of Pathways
• PROBLEMS Indiscriminate Activation
• Stimulation indiscriminately affects all tissue
  around the electrode (size 1.27mm diameter with
  four 1.5mm contacts)
• Crude method without feedback
• IMPROVEMENTS
• Targeted Activation to specific location down to
  sub mm scale
• Obtain feedback information such as
  neurotransmitter levels

Medtronic
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Current Techniques for Electrochemical Monitoring
of Neurotransmitters with Carbon Fiber Electrodes

• HOW Cyclic Voltammetry (CV)
• Carbon fiber micro-electrodes (10um dia.)
• Best detection is 500nM with temporal resolution
  of tens of milliseconds
• Most neurotransmitters are electrochemically
  active (i.e. dopamine glutamate)
• IMPROVEMENTS Requirements for Electrodes
• Ultrahigh sensitivity 1 nM
• Fast speed 10 ms resolution
• Good for long-term implantation

R.Mark Wightman, Analytical Chemistry, 414A (Oct.
2003).
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Vertical Aligned CNT Array A Novel Electrical
Neural Interface
Three-dimensional neural network
Micro- electrode Array (MEA)
Microelectrode
50 mm
Bionic Technologies Inc.
10 micron
Nanoelectrode Array (NEA)
NEA
2 mm
500 nm
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Goal To Develop an Integrated Multiplex Chip as
an Implantable Device for DBS and
Electrochemical Recording
Active Electrode Array at the Tip
200 mm
Medtronic
1 mm
2 mm
Possible Applications Parkinsons
Disease Epilepsy Other Neurological Disorders
Stimulating Electrode uncoated CNTs with large
surface area
Recording Electrode embedded in SiO2 with
ultrahigh sensitivity
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Health and Medicine
New formulations and routes for drug delivery,
optimal drug usage More durable,
rejection-resistant artificial tissues and
organs, implantable electrodes Sensors for
early detection and prevention
Expanding ability to characterize genetic
makeup will revolutionize the specificity of
diagnostics and therapeutics - Nanodevices can
make gene sequencing more efficient Effecti
ve and less expensive health care using remote
and in-vivo devices
Nanotube-based biosensor for cancer diagnostics
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CNT Based Biosensors
Probe molecules for a given target can be
attached to CNT tips for biosensor
development Electrochemical approach
requires nanoelectrode development using
PECVD grown vertical nanotubes The signal can
be amplified with metal ion mediator
oxidation catalyzed by Guanine.
High specificity Direct, fast
response High sensitivity Single molecule
and cell signal capture and detection
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Nanoelectrode Array (NEA)

• Break a solid micro- or macro electrode into an
  array of 100 to 109 nanoelectrodes
• Each electrode is well separated with the
  neighbors (gt 6R) so that the NEA behaves similar
  to a single NE.
• Can further create an individually addressed
  multiplex array in an array-in-array format

Challenges Reliable fabrication techniques with
affordable cost, particularly for low-density
NEAs.
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Electrochemical Detection by AC Voltametry
J. Li, H. T. Ng, A. Cassell, W. Fan, H. Chen, J.
Koehne, J. Han, M. Meyyappan, Nano. Lett., 2003,
3, 597.
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Fabrication of Genechip

• Potential applications
• Lab-on-a-chip applications
• Early cancer detection
• Infectious disease detection

30 dies on a 4 Si wafer
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Conceptual Immunosensor Chip for Bacteria
Monitoring
Reagent Pumping
Chip size 1x3

• 100 mL water sample w/ 100 bacteria filtered and
  condensed by 100 times into 1 mL solution
• 1 mL condensed solution passed by parallel
  microfluidic channels of 5 to 10 mm with
  multiplex NEAs.
• Bacteria trapped on some NEAs in corresponding
  zones assisted with dielectrophoresis
• Electrochemical detection done by a computer with
  multiplex interface cards

Goal (1) Detect 100-1000 bacteria/L in 10-20
minutes (2) Can detect upto 30 types of
bacteria
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Health and Medicine
New formulations and routes for drug delivery,
optimal drug usage More durable,
rejection-resistant artificial tissues and
organs, implantable electrodes Sensors for
early detection and prevention
Expanding ability to characterize genetic
makeup will revolutionize the specificity of
diagnostics and therapeutics - Nanodevices
can make gene sequencing more
efficient Effective and less expensive health
care using remote and in-vivo devices
Nanotube-based biosensor for cancer diagnostics
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DNA Sequencing with Nanopores
The Concept

• Nanopore in membrane (2nm diameter)
• DNA in buffer
• Voltage clamp
• Measure current

G. Church, D. Branton, J. Golovchenko, Harvard D.
Deamer, UC Santa Cruz
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The Sequencing Concept
Present
Future
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Summary
Nanotechnology is an enabling technology that
will impact almost all economic sectors one of
the most important and with great potential is
the health/medical sector. - Nanomaterials for
drug delivery - Early warning
sensors - Implantable devices - Artificial
parts with improved characteristics Opportuniti
es and rewards are great and hence, tremendous
worldwide interest