School of Biomedical Engineering, Science

1
School of Biomedical Engineering, Science
Health Systems
Nanotechnology Dialog with Lockheed Martin Team

• by
• Kambiz Pourrezaei, Professor

2
Outline
Presentation Outline

• Nanobiosensor Research R. Lec
• Nanoscale Microecapsulation Research M.
  Wheatley
• Nanoscale Q-Dot Research M. Papazoglou
• Nanoprobe Research K. Pourrezaei
• Nanoscale X-Ray Imaging Research C. Chang
• Nanobiomechanis Research K. Barbee
• Nanotissue Engineering Research P. Lelkes

3
Novel Applications of Piezoelectric Nanobiosensor
Technology
NANOBIOSENSOR RESEARCH

• DNA sensors/chips genetic screening and
  diseases, drug testing, environmental monitoring,
  biowarfare, bioterrorism, other.
• Immunosensors HIV, hepatitis, other viral
  diseases, drug testing, environmental monitoring,
  biowarfare, bioterrorism, other.
• Cell-based sensors functional sensors, drug
  testing, environmental monitoring, biowarfare,
  bioterrorism, other.
• Point-of-care sensors blood, urine,
  electrolytes, gases, steroids, drugs, hormones,
  proteins, other.
• Bacteria sensors (E-coli, streptococcus, other)
  food industry, medicine, environmental, other.
• Enzyme sensors diabetics, drug testing, other.
• Market clinical diagnostic, environmental
  monitoring, biotechnology, pharmaceutical
  industry, food analysis, cosmetic industry,
  other.
• Immunosensors about 1 billion annually.
• DNA probes about 1.5 billion annually.

4
The Challenges
NANOBIOSENSOR RESEARCH (Continued)

• Design and fabricate biologically active sensing
  interfaces DNA, proteins, cells, tissues, other.
• Integration of biological, physical (mechanical,
  optical, acoustic) and electronic components into
  multifunctional biosensor systems novel
  immobilization techniques solid-state transducer
  nano/microfabrication technologies microfluidic
  systems IC circuits for signal conditioning and
  processing smart biosensors and biosensor
  systems.

5
Development of Piezoelectric Nano-biosensor
Technology Platform
NANOBIOSENSOR RESEARCH (Continued)

• Important Features
• Multidomain Piezoelectric Sensing Mechanisms
  mass, viscosity, elasticity, electric
  conductivity, and dielectric constants.
• Real-time Piezoelectric Monitoring of Interfacial
  Biological Phenomena the depth of monitoring
  ranges from a single to hundreds nanometers with
  the time resolution of milliseconds.
• Piezoelectric Biotransducer Technology IC
  compatible, MEMS/NEMS sensing and actuating
  multiple-sensing- wave transducers,
  piezo-bio-chips and arrays, other.
• Bio-Piezo-Interfaces design and synthesis of
  surfaces at the atomic level to produce sensing
  interfaces with desired properties and functions.
• Integrated Electronic Signal Processing and
  Display Technologies fast, miniature,
  inexpensive, reliable.
• Smart Biosensors self-calibration,
  self-diagnostic, self-repair, other.

6
Development of Piezoelectric Nano-biosensor
Technology Platform (Continued)
NANOBIOSENSOR RESEARCH (Continued)
7
Piezoelectric Interfacial NanoBioSensor (PINBS) -
II
NANOBIOSENSOR RESEARCH (Continued)
PLAGA Nanofiber-based Biosesnor Interface
The PINBS response To the nanofiber loading.
Endothelial Cell on PLAGA Nanofiber Interface(
initial stage) and after 2 hours ( nicely
spread).
8
Endothelial Cell Properties Such As
Sedimentation, Adhesion, Proliferation and
Fixation
NANOBIOSENSOR RESEARCH (Continued)
Sedimentation, adhesion and proliferation
profile of endothelial cells as a function of
time measured using 25 MHz piezoelectric resonant
sensor.
9
Concept of Nano Contrast
NANOSCALE MICROECAPSULATION RESEARCH
10
Development and Characterization of a Nano-scale
Contrast Agent
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
Objective To test the feasibility of creating a
surfactant-stabilized nano-bubble with favorable
acoustic properties to act as an ultrasound
contrast agent that targets tumors.
Nano Pros and Cons

• Cons
• US reflection proportional to r6
• Resonance
• fo 6500/d kHz
• 1? 6.5 MHz but
• 0.1 ? 65 MHz
• More prone to removal by RES

• Pros
• Current agents are micro size, good to stay in
  vasculature, for nano, extravazation and pooling
  in tumor

11
In Vitro Setup
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
12
In Vivo Results
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
13
PIHI
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
14
Q-dots As Probes of Cellular Pathways
NANOSCALE Q-DOT RESEARCH
What are the Q-dots? The quantum dots (Evident
Technologies) are semiconductor nanocrystals
(diameter 2-10 nm) made from CdSe with an outside
shell of ZnS. Their size and their surface
chemistry are the main determinants of their
optical, electronic, and chemical properties. We
used Carboxyl and Amine terminated Qdots with
diameters of 20-30 nm.
Preliminary Experiments

• Cell Types Bovine Aortic Endothelial Cells
  (BAEC) and Human Ductile
• Carcinoma Cells (HDC)
• Q-dots Lake Placid Blue (AT and CT terminated)
• Techniques Syringe loading and Q-dot coating
• Live/dead assay Calcein AM and Ethidium
  homodimer-1

15
How Do Particles of This Size Interact With Cells?
NANOSCALE Q-DOT RESEARCH (Continued)

• Valuable model system due to fluorescence can
  guide the understanding of other nanosystems.
• Two types of cell cultures
• 1. Bovine aortic endothelial cells (BAEC).
• 2. Ductal carcinoma cells cancer cells.
• Plate-coated with Q-dot solution.
• With or without collagen culture cells.
• Trypsinize centrifuge.
• Fluorescence Microscopy to see if the cells
  did in fact uptake the Q-dots.

16
Absorption and Emission Spectra
NANOSCALE Q-DOT RESEARCH (Continued)
17
Preliminary Experiments
NANOSCALE Q-DOT RESEARCH (Continued)

• Cell Types Bovine Aortic Endothelial Cells
  (BAEC) and Human Ductile
• Carcinoma Cells (HDC)
• Q-dots Lake Placid Blue (AT and CT terminated)
• Techniques Syringe loading and Q-dot coating
• Live/dead assay Calcein AM and Ethidium
  homodimer-1

BAEC
Phase Contrast (40X)
Fluorescence (40X)
18
How Do Particles of This Size Interact With Cells?
NANOSCALE Q-DOT RESEARCH (Continued)
BAEC Qdots Lake Placid Blue CT - Phase
Contrast 40X Gelatin coated 25 well plate
transferred cells-Nikon Inverted - FITCI
BAEC Qdots Lake Placid Blue CT -
Fluorescence 40X Gelatin coated 25 well plate
transferred cells-Nikon Inverted - FITCI
19
Cancer Cells and Q-dots
NANOSCALE Q-DOT RESEARCH (Continued)
Cancer Cells Qdots Lake Placid Blue CT -
Phase Contrast 40X Gelatin coated 25 well plate
transferred cells-Nikon Inverted - FITCI
Cancer Cells Qdots Lake Placid Blue CT -
Fluorescence 40X Gelatin coated 25 well plate
transferred cells-Nikon Inverted - FITCI
20
High Spatial and Spectral Resolution X-ray
Microscope
NANOSCALE X-RAY IMAGING RESEARCH
We expect to be able to achieve 10 frames of live
biological samples before we exceed the threshold
of radiation dosage that is tolerable for these
biological samples. One strategy is to increase
the number of frames after exceeding the
allowable dosage to move to the previously
unexposed neighboring region.
Nanometer spatial resolution (20nm) over 10
micrometer x 10micrometer field of view detected
with 5nm x 5nm pixel size.
21
Human Monocytic Cell
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
X-ray microscope image of a human monocytic cell.
This cell is imaged in suspension.
22
Rat Adrenal Endothelial Cell
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
X-ray microscope image of a rat adrenal
endothelial cell. The cells are cultured on a
slab of thin (100nm) silicon nitride membrane,
which also serves as a sample holder for the
x-ray microsocpe.
23
Estimated Exposure Time for Undulator-based X-ray
Microscopes
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
24
Automated High Throughput Platform
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
Silicon nano fluidics channel
Silicon nano array
25
Magnetized Islands Attract Ferrofluid
NANO SCALE BIOMECHANICS RESEARCH (Continued)
Magnetized islands attract ferrofluid to one pole
in the presence of an external field
perpendicular to the surface.
6 Microns
40 Microns
26
Application of An External Field in the
Longitudinal Direction
NANO SCALE BIOMECHANICS RESEARCH (Continued)
When an external field is applied in the
longitudinal direction, the space between the
islands is masked.
27
High Aspect Ratio Gold Nanotopography
NANO SCALE BIOMECHANICS RESEARCH (Continued)
High aspect ratio gold nanotopography cells do
not adhere.
10 Microns
Cells on Smooth Gold
28
Cellular Tissue Engineering Primary Target
Tissues / Organs
NANOTISSUE ENGINEERING RESEARCH
29
In vitro Tissue Engineering
NANOTISSUE ENGINEERING RESEARCH (Continued)

• Macro- / Micro-scale for Individual Components
• Cells Cell Aggregates.
• Scaffolds Fibrous, Textured.

• In vivo NanoScale Cellular Action
• Cell-ECM communications are on the nano-scale.

30
Induction of Myocyte Differentiation By
Electrical Stimulation
NANOTISSUE ENGINEERING RESEARCH (Continued)

• Conductivity Carbon Nanoparticles
• Cells Cardiac Myocyte Precursors

31
Nanotechnology-based Elastomeric Vascular Graft
NANOTISSUE ENGINEERING RESEARCH (Continued)
Width 18 ?m Depth 500 nm
Width 3.3 ?m Depth 100 nm

• Composition
• Substrate polydimethylsiloxane (PDMS) (Sylgard
  184)
• Self-assembled monolayer 3-(triethoxysilyl)propy
  lsuccinic anhydride (TESPSA) (carboxylic acid
  terminated)
• Peptide RGD

• Texture Smooth Coarse
  Fine

PDMS
TESPSA-PDMS
RGD-PDMS
32
Electrospinning of Conducting Nanofibrous
Scaffolds
NANOTISSUE ENGINEERING RESEARCH (Continued)

• Unique Features
• Use of electroactive, nanofibrous scaffolds for
  tissue engineering purposes.
• Capability of generating oriented / aligned
  scaffolds.
• Electrospinning of pure PANi nanofibers /
  scaffolds.
• Co-electrospinning of natural ECM proteins
  (collagen) / biodegradable polymers.
• Generation of novel electroactive scaffolds by
  co-electrospinning of PLA with carbon
  nanotubes.

33
Tissue Engineering of Fetal Mouse Lung Using
Collagenous Scaffolds
NANOTISSUE ENGINEERING RESEARCH (Continued)
Nanofibrous matt (fiber diameter lt 100 nm).
Porous foam (pore size equals 10 nm).
34
Drexel BIOMED
Thank You!
Contact Information3141 Chestnut
StreetPhiladelphia, PA 19104Phone
215-895-2215Fax [phone]Email
biomed_at_drexel.edu

• Visit us on the web at

WWW.BIOMED.DREXEL.EDU