Title: School of Biomedical Engineering, Science
1School of Biomedical Engineering, Science
Health Systems
Nanotechnology Dialog with Lockheed Martin Team
- by
- Kambiz Pourrezaei, Professor
2Outline
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
3Novel 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.
4The 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.
5Development 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.
6Development of Piezoelectric Nano-biosensor
Technology Platform (Continued)
NANOBIOSENSOR RESEARCH (Continued)
7Piezoelectric 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).
8Endothelial 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.
9Concept of Nano Contrast
NANOSCALE MICROECAPSULATION RESEARCH
10Development 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
11In Vitro Setup
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
12In Vivo Results
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
13PIHI
NANOSCALE MICROECAPSULATION RESEARCH (Continued)
14Q-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
15How 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.
16Absorption and Emission Spectra
NANOSCALE Q-DOT RESEARCH (Continued)
17Preliminary 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)
18How 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
19Cancer 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
20High 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.
21Human Monocytic Cell
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
X-ray microscope image of a human monocytic cell.
This cell is imaged in suspension.
22Rat 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.
23Estimated Exposure Time for Undulator-based X-ray
Microscopes
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
24Automated High Throughput Platform
NANOSCALE X-RAY IMAGING RESEARCH (Continued)
Silicon nano fluidics channel
Silicon nano array
25Magnetized 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
26Application 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.
27High Aspect Ratio Gold Nanotopography
NANO SCALE BIOMECHANICS RESEARCH (Continued)
High aspect ratio gold nanotopography cells do
not adhere.
10 Microns
Cells on Smooth Gold
28Cellular Tissue Engineering Primary Target
Tissues / Organs
NANOTISSUE ENGINEERING RESEARCH
29In 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.
30Induction of Myocyte Differentiation By
Electrical Stimulation
NANOTISSUE ENGINEERING RESEARCH (Continued)
- Conductivity Carbon Nanoparticles
- Cells Cardiac Myocyte Precursors
31Nanotechnology-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
32Electrospinning 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.
33Tissue 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).
34Drexel BIOMED
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