Nano-Biotechnology

Applications
Linnea Fletcher, Ph.D.

Regional Director
Bio-Link South Central Region
Austin Community College
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 Topics
– Definition and Description
– Size Range
– Brief History
– Biological Systems
– Current Applications
– Economic and Social Factors
– Environmental Impact
– The Future of Nano-Biotechnology

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 Definition and Description

“At present, nanobiotechnology is a field that concerns the utilization

of biological systems optimized through evolution, such as cells,
cellular components, nucleic acids, and proteins, to fabricate
functional nanostructured architectures comprised of organic and
inorganic materials.”

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 Size Range
Units of Measure:
• 1 nanometer or 1nm = 10-9 meters (m) = 10-6 millimeters (mm) =
10-3 micrometers (µm)
• 1 Angstrom, 1Ǻ = 10-10 m or 10,000,000,000Ǻ = 1 meter or 10+10Ǻ

Can you convert 600 nm to µm & Ǻ?

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 Size Range, Continued
Biomolecules are Nanoscale
Object Diameter (nm) Inside diameter
(nm)
Hydrogen atom 0.1
Water molecule 0.3
DNA (width) 2.5
Cell membrane 5-9
Porin channel 4-10 2-3
Actin filament 5-9
Microtubule 25 12-15
Bacterial flagellum 12-25 2-3
Magnetosome 35-150
crystals
Liposome vesicle 100 (minimum) 85 (minimum)
Bacterial cell 250 (minimum
1,000 (maximum)
Spores 1,000-8,-000
Red blood cell 6,000-8,000
Human hair 100,000

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 Size Range, Continued
Comparison of Size

Figure 9.1: Relative sizes of biological elements.

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 Brief History

“There is plenty of room at the bottom.”

Dr. Richard Feynman, 1959

Father of Nanotechnology

Figure 9.2: Dr. Richard Feynman

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 Brief History, Continued
Semiconductor Industry as Incubator

• Scanning Tunneling
Microscopy
- Resolution of 1/100 of
an atom.

Figure 9.3: Schematic view of a STM.

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 Brief History, Continued
Scanning Probe

• Atomic Force Microscopy

- Produces 3-D images.
- Resolution 1/100 of an atom.

Figure 9.4: Block diagram of Atomic Force

Microscope.

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 Brief History, Continued
Semiconductor Chips
• Borrowing from the semiconductor industry, researchers are
developing chips that can be used diagnostically.

Figure 9.5: Semiconductor chips. Figure 9.6: Diagnostic semiconductor chips.

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 Biological Systems
• Modular and Replaceable Parts
• Molecular Motors with Specific Targeting
• Durable
• Catalytic at Ambient Temperatures
• “Bottom-Up” Manufacturing
• Self-Assembly
• Genetically Re-Engineered
• Mass Produced

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 Biological Systems, Continued
Modular and Replaceable Parts

Figure 9.7: Nature provides examples of nanoscale actuators and pumps.

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Biological Systems, Continued
Molecular Motors with Specific Targeting
• Examples include circular, linear, and antibodies.

Figure 9.8a: Example of a molecular linear motor. Figure 9.8b: Antibody.

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 Biological Systems, Continued
Durable

Organisms can live in

hostile environments; they
possess proteins and other
components that can
withstand extreme
conditions.

Figure 9.9: Taq DNA polymerase.

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Biological Systems, Continued
Catalytic at Ambient Temperatures
• DNA and RNA polymerases in your body temperature
(37oC) work as fast as a jet engine!
• Go to www.dnai.org, DNAi, a product of the Dolan DNA
Learning Center at Cold Spring Harbor, and view the
animations for DNA replication, transcription and
translation.

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Biological Systems, Continued
“Bottom-Up” Manufacturing

• DNA mRNA protein

• Eukaryotes
DNA (exons and introns)

• Final mRNA is composed

of exons.

• cDNA is complementary to
mRNA.
Figure 9.10: Transcription and Translation.

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 Biological Systems, Continued
Self-Assembly
Self-assembly is assembly of molecules without use of outside
source.
Examples:
• Many proteins assembly while being synthesized.
• Some can reassemble after being denatured (e.g. the
enzyme, super oxide dismustase or SOD.
• This enzyme allows “life” to live in the presence of
chemically-harmful properties of oxygen.

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 Biological Systems, Continued
Self Assembly, Continued

Hydrophilic Head

Hydrophobic
Tail
Figure 9.11a: Amphiphilic
molecules.

Water Figure 9.11b: Micelles.

Figure 9.11c: Self assembly.

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Biological Systems, Continued
Genetically Engineered
• Genetic engineering of
insulin – what does it mean?

Figure 9.12: Insulin DNA.

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 Biological Systems, Continued
Genetically Re-Engineered, Continued
• Site-Directed Mutagenesis

Figure 9.13: Site-directed mutagenesis.

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Biological Systems, Continued
Genetically Re-Engineered, Continued
•Tailor-Made Proteins: Changing Amino Acids

Figure 15: Changing amino acids.

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Biological Systems, Continued
Mass-Produced

Figure 9.15: Monoclonal antibody production.

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 Current Applications
• In Vitro Biological Screening
- DNA, Hybridization, Detector Arrays
• Lab-On-A-Chip
- PCR, Molecular Diagnostics, CF
• Drug Delivery and Targeting
• In Vivo Molecular Medicine
- Quantum Dots
• Sensors
• Smart Medical Devices
- Dental, Glucose, Electric Nose
• Tissue Engineering
- Implants/Transplantation
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Current Applications, Continued
In Vitro Biological Screening
• Basic research with medical applications.

Figure 9.16: Two Affymetrix chips.

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Current Applications, Continued
In Vitro Biological Screening, Continued
• Gene Expression

Figure 9.17: Through the processes of

transcription and translation, information
from genes is used to make proteins.

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Current Applications, Continued
In Vitro Biological Screening, Continued
• Hybridization

Definition: Process of joining two

complementary strands of DNA to form
double-stranded molecule.

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Current Applications, Continued
In Vitro Biological Screening, Continued
• Detector Array

Detector
Probe Array
Laser
Hybridized Array

Tagged RNA Target

Fluorescent
Stain

Figure 9.18: Detector Array: one grey square = one feature; millions on a chip.

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Current Applications, Continued
Lab-On-A-Chip
• Advantages
- Small Sample Size
- Does Not Require Refrigeration
- Test Could Possibly Be Done at Home
- Chip Tests Could Be Embedded In A Person (In Vivo)

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Current Applications, Continued
Lab-On-A-Chip, Continued
• PCR Reaction

Figure 9.19: Polymerase Chain Reaction (PCR).

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Current Applications, Continued
Lab-On-A-Chip, Continued
• Molecular Diagnostics
- Cystic Fibrosis
• Symptoms
- Respiratory Infections
- Pancreatitis
- Abnormal Heart Rhythms

Figure 9.20a: Human Respiratory System.

Figure 9.20b: Location of the CFTR gene on chromosome 7.

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Current Applications, Continued
Lab-On-A-Chip, Continued
• Molecular Diagnostics, Continued
- Cause and Treatment of CF
• Caused by a Defective Gene
• Research and Treatment
– Gene Therapy: Inhaler That Delivers “DNA”

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 Current Applications, Continued
Drug Delivery and Targeting
• Drug Delivery
- Liposomes:
Microscopic fluid-filled pouches.

Could be used to release

anticancer or antimicrobial
compounds.
• Drug Targeting
- Recognition:
Target specific cell types
Figure 9.21: Phospholipid drug delivery.
based on surface proteins.

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 Current Applications, Continued
In Vivo Molecular Medicine
• Quantum Dots
- Definition: About a single
nanometer in size and made out of
material such as silicon.
- Quantum effects arise from
confinement of electrons and
“holes” (absence of electrons).
- Hold promise of new
emitter/detector technology.
- Size determines color. Figure 9.22: CdSe quantum dot
fluorescence showing an increase in dot
size going from green on the left to red on
the right.

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Current Applications, Continued
Sensors
• Biosensors: Bacteria that can locate biologically active
pollutants.
• Bioluminescence: Reports presence of a pollutant.

Figure 9.23: Omphalotus nidiformis, glowing with the lights off bioluminescence.

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Current Applications, Continued
Smart Medical Devices
• Smart Tools
- Tools that detect and react, or
“embedded smarts and intelligence.”

- Dental: “Smart” Filling.

Photo credit: NIST

Figure 9.24: A calcium

phosphate nanocomposite filling
in a tooth.

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Current Applications, Continued

Smart Medical Devices, Continued

• Glucose Sensing
- Blood Glucose Meters:
Small computerized machines that “read”
blood glucose.

- Better Than Traditional Finger Stick.

Figure 9.25: Blood glucose

testing.

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Current Applications, Continued

Smart Medical Devices, Continued

Glucose Sensing, Continued
• FreeStyle Navigator System
- Three-Part System:
• PART I - Sensor
• PART II - Wireless Transmitter
• PART III - Receiver
• Lifescan CGM – Measures ISF transdermally.

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Current Applications, Continued
Smart Medical Devices, Continued
• Other Glucose Sensors

Figure 9.26: Glucose sensor is an enzyme.

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Current Applications, Continued

Smart Medical Devices, Continued

• Glucose Delivery

- Injections vs. Insulin Pump

- All-In-One: Sensing and Delivery
• Medtronic Mini-Med Paradigm ® Real-time continuous
glucose monitoring/delivery device.

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Current Applications, Continued

Smart Medical Devices, Continued

• Electronic Nose
- Sandia Labs in New Mexico –
Sandia Hound.
- Owlstone in Cambridge –
Sensor that can be altered.
- SPOT-NOSED Project –
Detects odorants at concentrations
that would be imperceptible to
humans.

Figure 9.27: Sandia National Laboratories

researcher Dave Hannum demonstrates use of
Hound system.

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Current Applications, Continued
Tissue Engineering
• Implants
- In retinal diseases, photoreceptor cells are destroyed.
- Artificial retina device transmits signals directly to optic nerve.
- Parts of artificial retina device:
• Camera and microprocessor mounted in eyeglasses.
• Receiver implanted behind ear.
• Electrode studded array tacked to retina.
• Wireless battery pack worn on belt for power.
• Sandia Labs working on battery that can be implanted in person’s
head.

4141
Current Applications, Continued
Tissue Engineering, Continued
• Artificial Retina and Pixel Resolution

Figure 9.28a: Artificial retina. Figure 9.28b: Pixelation.

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Current Applications, Continued
Tissue Engineering, Continued
• Transplantation
- Stem Cells
- Changing one cell type to another type
• Nuclear
• Virally-Induced
• Transplant Issues
• Not Enough Organs
• Growing Organs
• Rejection

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Current Applications, Continued
Tissue Engineering, Continued
• Stem Cell Issues
- Embryonic stem cells can become all
cell types of the body because they are
pluripotent.
- Adult stem cells are multipotent,
meaning they can yield all of the cell
types associated with the tissues from
which they originate.

Figure 9.29: Human embryonic stem cell colony on

mouse embryonic fibroblast feeder layer.

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Current Applications, Continued

Tissue Engineering, Continued

• Stem Cell Issues, Continued
- Somatic Cell Nuclear Transfer (SCNT) – Substitutes
the nucleus of a somatic cell (which contains all the
genetic information of the patient) for the nucleus of a
donated egg that has not been fertilized.

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Current Applications, Continued

Tissue Engineering, Continued

• Changing Cellular Identities

Figure 9.30: Hepatocyte to beta cell.

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Current Applications, Continued

Tissue Engineering, Continued

• Transplant Issues
- Shortage of donor organs.
- Tissue engineering lab at
Massachusetts General Hospital.
• Hepatocytes – liver cells.

Figure 9.31: Transplant issues.

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Current Applications, Continued

Tissue Engineering, Continued

• The “Islet Cell” Capsule at John Hopkins University
- Protects the cells from rejection and at the same time
allows for visualization.
- Implanted in the liver.

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Economic and Social Factors

Areas of Use
• Agricultural Biotechnology
• Environmental Testing
• Food Testing
• Livestock Diagnostics
• Identity Testing
• Individualized Medicine
• Human Diagnosis
• Basic Research

Figure 9.32: Diagram of typical dual-color

microarray.

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 Economic and Social Factors,
Continued
Ethical Issues
• Should we screen newborns
before birth for conditions and
diseases?
• Will everyone have access to
screening?
• What are social implications of
newborn screening?

Figure 9.33: Obstetric sonogram

of a fetus at 16 weeks.

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 Environmental Impact
Agencies Charged with Developing Standards for Quality
Assurance and Control of Nanotechnology Products.

• Environmental Protection
Agency (EPA)
• U.S. National Institute of
Standards and Technology
• University of Florida
Nanotoxicology Group

Figure 9.34: International Symbol for Poison.

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The Future of Nano-Biotechnology
Diagnostic vs. Therapeutic Medicine
• Why play “catch-up” when you can prevent it or diagnose it
early and fix it fast!

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