In recent years there has been ever increasing activity and interest within the scientific and engineering fields about engineered nanoparticles (ENP). PerkinElmer's analytical instruments enable engineers and scientists to measure, characterize, and better understand nanomaterials for industrial and academic nanotechnology research. In this Nanotechnology Insights e-Zine you will find a wide range of solutions and scientific papers about nanomaterial applications (from synthesizing to end use) that illustrate PerkinElmer's support and contribution to customers working in this revolutionary science.

1. TABLE OF CONTENTS
NANOTECHNOLOGY
INSIGHTS

2. TABLE OF CONTENTS
INTRODUCTION
In recent years there has been ever increasing activity and interest within the scientific
and engineering fields about engineered nanoparticles (ENP). PerkinElmer’s analytical
instruments enable engineers and scientists to measure, characterize, and better
understand nanomaterials for industrial and academic nanotechnology research. In this
Nanotechnology Insights e-Zine you will find a wide range of solutions and scientific
papers about nanomaterial applications (from synthesizing to end use) that illustrate
PerkinElmer’s support and contribution to customers working in this revolutionary
science.
Read, Learn, and Share!
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3. TABLE OF CONTENTS
CONTENTS
Fundamental Concepts
• Frequently Asked Questions- Nanotechnology and Engineered
Nanomaterials
• Nanopharmaceuticals and PerkinElmer
Thermal Analysis
• Improved HyperDSC Method to Determine Specific Heat Capacity of Nanocom-
posites and Probe for High-Temperature Devitrification
• A Study of Aged Carbon Nanotubes by Thermogravimetirc Analysis
Molecular Spectroscopy
• Simple Method of Measuring the Band Gap Energy Value of TIO2 in the Pow-
der Form using a UV/Vis/NIR Spectrometer
Atomic Spectroscopy
• Analysis of NIST Gold Nanoparticles Reference Materials Using the
NexION 300 ICP-MS in Single Particle Mode
• Colorado School of Mines Uses a NexION 300Q ICP-MS to Obtain a Better
Understanding of the Impact of Engineered Nanomaterials
Hyphenated Techniques
• An Introduction to Flow Field Flow Fractionation and Coupling to ICP-MS
• Coupling Flow Field Flow Fractionation to ICP-MS for the Detection and
Characterization of Silver Nanoparticles
• Characterizing Interaction of Nanoparticles with Organic Pollutants Using
coupling Thermal Analysis with Spectroscopic Techniques
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4. TABLE OF CONTENTS
Fundamental Concepts
• Frequently Asked Questions- Nanotechnology and Engineered
Nanomaterials
• Nanopharmaceuticals and PerkinElmer

5. Frequently
Nanotechnology and
TABLE OF CONTENTS
asked
questions Engineered Nanomaterials
A Primer
authors:
Andrew W. Salamon, Patrick Courtney and Ian Shuttler
Introduction
In recent years there has been ever increasing activity and excitement within the scientific
and engineering communities, driven heavily by government investment, about engineered
nanotechnology applications. The U.S. National Science Foundation has estimated that
the global nanotechnology market could be worth U.S.$1 trillion by 2015.1 In parallel,
much has been written and presented about the excitement and possible dangers of these
materials. The tone of these media articles range from how these wonder materials are
going to revolutionize all aspects of our lives to how they might kill us! The purpose of
this primer is to provide some basic information about engineered nanomaterials so that
you will be better informed, understand the new ‘jargon’ and appreciate some of the
potential new applications of these materials. In addition, understanding the wide range
and types of measurements needed to characterize these nanomaterials along with what
solutions PerkinElmer has to support customers working in this field are outlined.
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6. Table of
TABLE OF CONTENTS
Contents
What is nanotechnology? 3
What is the market and potential of nanotechnology? 4
What are engineered nanomaterials? 4
Fullerenes, graphene and carbon nanotubes 5
Quantum dots 5
Nanoparticles 6
Nanofibers and Nanowires 6
Where are nanomaterials being used today and in the future? 7
How are nanomaterials characterized? 7
What analytical techniques are used to characterize nanomaterials? 12
What are the environmental implications of nanotechnology? 13
What solutions are provided by PerkinElmer for nanomaterials
characterization? 15
Where can I find more information? 16
References 16
Useful books and websites for more information 19
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7. Q What is nanotechnology?
A Nanotechnology is the science and technology of precisely manipulating the struc-
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ture of matter at the molecular level. The term nanotechnology embraces many
different fields and specialties, including engineering, chemistry, electronics, and
medicine, among others, but all are concerned with bringing existing technologies
down to a very small scale, measured in nanometers.2 Processes and functionality
take place at the nanoscale, exhibiting properties not available in the bulk mate-
rial. But what is a nanometer? Figure 1 compares the nano-region to things we
know, such as a pin, insect and cells and provides a visual perspective.
Figure 1. Size relationships from large to small to nano.
A nanometer is a thousandth of a micron and a micron is a thousandth of a millimeter,
so a nanometer is a millionth of a millimeter or 10-9 meters. To be classified as a
nanomaterial (NM), the material must be less than 100 nm in size in at least one
direction. According to the International Standards Organization® (ISO) a nano-object
is a material with at least one, two or three external dimensions in the nanoscale
range of 1 to 100 nm and a nanoparticle is a nano-object with all three external
dimensions in the 1 to 100 nm range and showing a property not evident in the
bulk material. Hence, a nanofiber, 400 nm long and 12 nm in diameter, and a
20 nm diameter nanoparticle, are both classified as nanomaterials.3
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8. Even though ISO does not distinguish between engineered nanoparticles and
naturally occurring nanoparticles, you should be aware that there are naturally
occurring nanoparticles in the aquatic environment such as biodegraded organic
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matter and colloidal inorganic species and in soils; clays, organic matter and various
metal oxides.4 Many important functions of living organisms take place at the nano-
scale. The human body uses natural nanoscale materials such as proteins and other
molecules, to control the body’s many systems and processes. A typical protein such
as hemoglobin, which carries oxygen through the bloodstream, is 5 nm in diameter.5
However, this primer concentrates on Engineered Nanomaterials (ENMs).
Q What is the market and potential of nanotechnology?
A
According to the U.S. National Nanotechnology Initiative (NNI), Federal Government
funding in the United States, for nanotechnology, has increased from approximately
$464 million in 2001 to nearly $1.9 billion for the 2010 fiscal year. Private industry is
investing at least as much as the government, according to estimates. The United States
is not the only country to recognize the tremendous economic potential of nanotech-
nology. While it is difficult to measure accurately, estimates from 2005 showed the
European Union (EU) and Japan are investing approximately $1.5 billion and $1.8 billion,
respectively, in nanotechnology. Behind them were Korea, China and Taiwan with
$300 million, $250 million and $110 million respectively, invested in nanotechnology
research and development.6
Last year the Russian government announced that it was investing $11 billion in an
ambitious plan to develop and commercialize nanotechnologies.7 It is not only gov-
ernments that are investing heavily in this area, venture capital firms invested $702M
in nanotechnology start-ups in 2007 across 61 investments. The Japanese Mitsubishi
Institute projected nanotechnology to be worth U.S.$150 billion on the global market
by 2010 and Lux Research® estimated a U.S.$2.6 trillion global market by 2014.1 The
U.S. NNI continues to be well funded with a 2010 budget of $1.6B, with total spending
since 2001 of nearly $14B. However, to put some of these numbers into perspective,
allocation of NNI funds for environmental, health and safety research since 2005
totals $480M.8 In spite of this it is clear that significant investments are being made
in all aspects of nanotechnology and that there is considerable potential.
Q What are engineered nanomaterials?
A There are many new material terminologies associated with this field. This section
gives a short overview of some of the different types of nanomaterials.
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9. Fullerenes, graphene and carbon nanotubes
A Fullerene is any molecule in the form of a hollow sphere, ellipsoid or tubular
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structure composed entirely of carbon. They are commonly referred to as
“Buckyballs” – named after Buckminster Fuller who designed geodesic physical
structures and buildings based on this geometry. A Buckyball is a carbon based
hollow geometric sphere, first found in soot developed from a laboratory experiment.
It resembles a hollow spherical geodesic dome and is comprised of 60 carbon
atoms (C60). Discovered in 1985, it is the roundest and most symmetrical large
molecule known to man.9 Fullerenes or Buckyballs
are used in nanotechnology. Graphene is a one atom
thick planar sheet of carbon atoms densely packed
in a honeycomb crystal lattice. Graphene is the basic
structural building block of carbon nanotubes and
fullerenes. Carbon nanotubes (CNT) also known as
‘buckytubes’ have a cylindrical nanostructure in the
form of a tube and an engineered CNT typically has a
nanoscale thick wall, geometrically shaped similar to
a Buckyball, with a nanoscale diameter, and a length Figure 2. C60 buckyball.
that may exceed 100 nm.
Carbon nanotubes are manufactured as single
wall carbon nanotubes (SWCNT) or multiwall car-
bon nanotubes (MWCNT). An example is shown
in Figure 3. They are synthesized in a variety of
ways, including arc discharge, laser ablation and
chemical vapor deposition. With respect to tensile
strength, carbon nanotubes are the strongest and
Figure 3. Multiwalled carbon stiffest materials yet discovered, more than 5 times
nanotube. stronger than Kevlar®. Since CNTs have a very low
density, their specific strength is 300 times greater
than stainless steel, though under compression CNTs appear to be a lot weaker.
Quantum dots
Quantum dots, also known as nanocrystals, are another form of nanomaterial and
are a specific type of semiconductor. They are 2-10 nanometers (10-50 atoms) in
diameter, and because of their electrical characteristics, they are [electrically] tun-
able.10 The electrical conductivity of semiconductors can change due to external
stimulus such as voltage or exposure to light, etc. As quantum dots have such a
5
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10. small size they show different properties to bulk material. Hence the ‘tunability’,
for example, sensitivity to different wavelengths of light, can be adjusted by the
number of atoms or size of the quantum dot. Quantum dots are typically made
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from CdSe, ZnS or CdTe compounds, though from a EU Restriction of Hazardous
Substances (RoHS) perspective, cadmium-free quantum dots are required.11 For an
excellent explanation of quantum dots and their operation in a cadmium selenide
semiconductor see the website associated with reference.10
Nanoparticles
Nanoparticles (NP) are synthesized or machined. They range in size from 2 nm
to 100 nm. Nanoparticle materials vary depending on their application. Because
Nanoparticles are invisible to the naked eye, they are usually supplied suspended
in a liquid. This is done for safety and handling reasons. Figure 4 shows gold
nanoparticles suspended in liquid. The color is due to the refraction of light the
surface area of the particular nanoparticle reflects. Different sized nanoparticles
exhibit different colors based on its surface area.12
Figure 4. Suspension of gold Figure 5. SEM image of aligned
nanoparticles. nanofibers. Photo courtesy of Univ.
of Wisconsin – Madison, Department
of Chemistry.
Nanofibers and Nanowires
Nanofibers are slightly larger in diameter than the typical nanomaterial definition,
though still invisible to the naked-eye. Their size ranges between 50 nm - 300 nm
in diameter and are generally produced by electro spinning in the case of inor-
ganic nanofibers or catalytic synthesis for carbon nanotubes. Figure 5 shows an
SEM image of aligned nanofibers. Nanofibers can be electrostatically aligned and
biochemically aligned.13,14 Further information about nanofibers fabrication can be
found in reference.15 Similar to nanofibers are nanowires, though nanowires are
considerably smaller in diameter, of the order of 4 nm and conduct electricity.
In Table 1, the different size characteristics of the various nanomaterials are
summarized.
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11. Table 1. Nanomaterial types and dimension characteristics.
Type of Nanomaterial Number of dimensions and size
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Nanoparticle Three dimensions in the 1 to 100 nanometers (nm) range
Nanotubes/nanowires Two dimensions in the 1 to 100 nm range
Nanofibers Length ranges between 50 nm and 300 nm with diameter <50 nm
Nanofilms One dimension in the 1 to 100 nm range
Nanoplates Two dimensions in the 1 to 100 nm range
Q Where are nanomaterials being used today and in the future?
A Some of the current applications of many of these nano-related materials and
technology are outlined in Table 2 (Page 8). While this table is not intended to be
exhaustive, it does show how wide ranging the applications are. It is clear that the
nanomaterial science revolution has the potential and magnitude to be an enormous
leap forward in technology. However, it should be noted that there are increasing
concerns about the impact of these materials in the environment and their possible
impact on human health.
Currently the Woodrow Wilson Center for Scholars through their Project on
Emerging Nanotechnologies (PEN) lists in their database, 1015 commercially available
nanotechnology containing consumer products in over 20 countries16 up to 2009.
This website and searchable database is recommended for those wishing to learn
more.
A more comprehensive listing of current and possible future applications of
nanomaterials is available on www.PerkinElmer.com/nano
Q How are nanomaterials characterized?
A It is important to understand that the excitement regarding the synthesis and
application of nanomaterials is based on the fact that, because of their very small
size, the characteristics and behavior are quite different to bulk materials with the
same composition. Consequently, the range of parameters that has to be assessed
to characterize these materials is large. Fundamentally there are seven key
characteristics that contribute to the uniqueness of nanomaterials and these
are summarized in Table 3.
In addition to the key seven characteristics, there are two additional qualities
that are unique to nanomaterials and important in characterizing them. These
are agglomeration, which is the tendency of the particles to clump together
and form larger combined particles, and the particle size distribution.
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12. Table 1. Nanomaterial types and dimension characteristics.
Type of Nanomaterial Number of dimensions and size
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Nanoparticle Three dimensions in the 1 to 100 nanometers (nm) range
Nanotubes/nanowires Two dimensions in the 1 to 100 nm range
Nanofibers Length ranges between 50 nm and 300 nm with diameter <50 nm
Nanofilms One dimension in the 1 to 100 nm range
Nanoplates Two dimensions in the 1 to 100 nm range
Q Where are nanomaterials being used today and in the future?
A Some of the current applications of many of these nano-related materials and
technology are outlined in Table 2 (Page 8). While this table is not intended to be
exhaustive, it does show how wide ranging the applications are. It is clear that the
nanomaterial science revolution has the potential and magnitude to be an enormous
leap forward in technology. However, it should be noted that there are increasing
concerns about the impact of these materials in the environment and their possible
impact on human health.
Currently the Woodrow Wilson Center for Scholars through their Project on
Emerging Nanotechnologies (PEN) lists in their database, 1015 commercially available
nanotechnology containing consumer products in over 20 countries16 up to 2009.
This website and searchable database is recommended for those wishing to learn
more.
A more comprehensive listing of current and possible future applications of
nanomaterials is available on www.PerkinElmer.com/nano
Q How are nanomaterials characterized?
A It is important to understand that the excitement regarding the synthesis and
application of nanomaterials is based on the fact that, because of their very small
size, the characteristics and behavior are quite different to bulk materials with the
same composition. Consequently, the range of parameters that has to be assessed
to characterize these materials is large. Fundamentally there are seven key
characteristics that contribute to the uniqueness of nanomaterials and these
are summarized in Table 3.
In addition to the key seven characteristics, there are two additional qualities
that are unique to nanomaterials and important in characterizing them. These
are agglomeration, which is the tendency of the particles to clump together
and form larger combined particles, and the particle size distribution.
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13. Table 2. Selection of nanomaterials and usage or application area.
Market Industry Type of Use/Application Area
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Segment Nanomaterial
Environmental Water Nano zero valent Being tested for the remediation of ground and surface waters
iron (nZVI) exposed to chlorinated hydrocarbons17
Gold nanoparticles Various gold nanomaterials are used to enhance imaging
properties of a variety of MRI and CT-based contrast agents18
UV absorbing Improved and sustainable water based surface coatings to
nanomaterials protect and preserve wood, concrete and metal surfaces used
in construction19
Safety and Food Clay Nanomaterials are being used in food packaging. The
Security penetration of light, moisture, or gases can alter the sensory
characteristics of food products, as well as increase spoilage.
Nanomaterials enhance packaging barrier properties20
Energy Pd and V doped Enhance hydrogen fuel cells by increasing storage capacities
carbon nanotubes and showing faster hydrogen absorption kinetics21
Medical Various materials Nanomaterials coated with pharmaceutical compounds are
being considered as novel inhalation delivery systems for
medications difficult to administer by other means22
Textiles/ Silver nanoparticles Integrated with sports clothing to prevent microbial growth,
Apparel and odor23,24
Cosmetics/ Nano titanium Used in some cosmetics. The applications include: eye liners,
Personal dioxide and nano moisturizers, lipsticks, make-up foundations, soaps, sunscreen,
Care Products zinc oxide mascara, and nail polish16
Industrial Defense CNTs Body armor – multilayer-epoxy composites manufactured with
CN sheets, the size of a piece of plywood 4’ x 8’ foot, provide
a shield that can stop a 9 mm bullet and weighs no more than a
pack of playing cards25
Aerospace Clay nanoparticles Incorporated with thermoplastics to create improved fire
retardant aircraft interiors26
Automotive 10 nm Cerium oxide Forms part of the Envirox™ diesel fuel catalyst which improves
nanoparticles combustion due to the increased surface area of the cerium
oxide nanoparticles27
Recreation/ Unknown Holmenkol® AG supply a chemical nanotechnology coating
Manu- system under the brand name ‘Nanowax®’ to replace conven-
facturing tional ski and snowboard waxes28
Sports CNTs/Yarn High end golf club shafts are made with nano-composites to make
equipment the shaft stronger and more flexible. Racing bicycle components29
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14. Table 3. Nanomaterial characteristics, their impact and importance.
Nanomaterial Characteristic Impact and Importance
TABLE OF CONTENTS
Size Key defining criteria for a nanomaterial3 (see Table 1).
Shape Carbon nanosheets with a flat geodesic (hexagonal) structure show improved performance
in epoxy composites versus carbon fibers.30
Surface Charge Surface charge is as important as size or shape. Can impact adhesion to surfaces and
agglomeration characteristics. Nanoparticles are often coated or ‘capped’ with agents such
as polymers (PEG) or surfactants to manage the surface charge issues.
Surface Area This is a critical parameter as the surface area to weight ratio for nanomaterials is huge.
For example, one gram of an 8 nm diameter nanoparticle has a surface area of 32 m2.
Nanoparticles may have occlusions and cavities on the surface.
Surface Porosity Many nanomaterials are created with zeolite-type porous surfaces. These engineered
surfaces are designed for maximum absorption of a specific coating or to accommodate
other molecules with a specific size
Composition The chemical composition of nanomaterials is critical to ensure the correct stoichiometry
has been achieved. The purity of nanomaterials, impact of different catalysts used in the
synthesis and presence of possible contaminants needs to be assessed along with possible
coatings that may have been applied.
Structure Knowledge of the structure at the nano level is important. Many nanomaterials are hetero-
geneous and information concerning crystal structure and grain boundaries is required.
Figure 6. Key parameters to characterize nanomaterials.
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15. Q What analytical techniques are used to characterize nanomaterials?
A As shown in Figure 6 there are seven key characteristics along with agglomeration
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and particle size distribution that need to be measured to fully describe a nano-
material. Consequently, at the nanoscale, analytical measurement challenges are
considerable and the ability to use, for example, one technique such as inductively
coupled plasma-mass spectrometry (ICP-MS) to measure the elemental concentration
of gold in a suspension of gold nanoparticles as the only metric to assess the
material, does not provide all the information needed. To completely characterize
the material it is necessary to know a multitude of chemical and physical parameters
including; the size of the particles, their shape, surface characteristics, presence
of any surface coating and presence of impurities. This small subset illustrates the
magnitude of the measurement challenge facing the nanomaterials industry. Table 4
lists the key characteristics and many of the current analytical technologies that
can be applied.
In addition to looking at a variety of analytical techniques and their application
to nanomaterials it is also important to understand where measurements need
to be made, what type of measurements are required and why. To understand
this, an overview of the nanomaterial manufacturing process and value chain is
necessary. This includes consideration of aspects such as source and quality of
raw materials, control of the synthesis/manufacturing process, validation of the
final product and subsequent use or incorporation into another product, e.g., a
cosmetic preparation. Along this manufacturing chain are a variety of points at
which material and hazardous waste may need to be disposed of and there is
potential for environmental exposure. Figure 7 provides a high level view of this
process in a very fast changing technology area and outlines which characteristics
may need to be assessed at the various measurement points. To understand which
analytical technologies may be required to provide this information, Figure 7 and
Table 4 can be compared. This chain has been developed from recent market
research and customer feedback.
Key nanomaterial characteristics require new measurement technologies. An analyti-
cal technique that is becoming more prevalent in the nanomaterial field is that of
Field Flow Fractionation (FFF) coupled with Light Scattering (LS) and possibly ICP-MS
for elemental nanoparticle characterization. Field Flow Fractionation is a separation
technique similar to chromatography whereby colloids, macromolecules and
nanoparticles are separated by size and should allow a separation of natural and
engineered nanomaterials. Further details can be found in a recent review article
on the coupling of FFF with ICP-MS31 and the websites under references.32,33
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16. TABLE OF CONTENTS
Figure 7. High-level overview of the engineered nanomaterial manufacturing process and key characteristics.
Electron microscopy is also widely used to characterize nanoparticles. The surface
area, porosity, particle shape, and agglomeration can be examined with Scanning
Electron Microscopes (SEM), Atomic Force Microscopes (AFM), Tunneling Electron
Microscopes (TEM), and Confocal Microscopes.
In the production and characterization of carbon nanotubes (CNTs) the use of
Thermogravimetric Analysis (TGA) has found considerable application and can be
used to show batch to batch reproducibility, detect changes in the process and
validate purification protocols.34 During both the production and formulation
process, many nanoparticles are coated or ‘capped’ with a variety of molecules.
For assessing the coating, the hyphenated technique of TGA coupled with GC/MS
is finding use.35 A critical application in this area is determining the amount of
anti-cancer drug that is coated on nanoparticles. This is needed to characterize
the dosage being consumed by the patient.
Q What are the environmental implications of nanotechnology?
A Process waste has always been a manufacturing issue. It is slightly different today
when nanoparticles are considered. Nano-waste is different than bulk material waste.
It’s been seen in laboratory experiments that nanomaterials can enter the human
body by dermal exposure, inhalation, and ingestion.36 While there are no specific
nanomaterials regulations, yet, there is increasing review and concern both within the
industry and in the environmental field as to the fate and behavior of these materials
in the environment. Many nanomaterial manufacturers are following bulk material
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17. Table 4. Nanomaterial characteristics and applicable analytical technologies.
Nanomateria
TABLE OF CONTENTS
Concentration Particle Size Particle Size Su
Analytical Technique Distribution Ch
Inductively Coupled Plasma – Mass Spectrometry ICP-MS
Field-flow Fractionation + ICP-MS FFF-ICP-MS
Liquid Chromatography – Mass Spectrometry LC-MS
Optical Spectroscopy – UV/Vis UV/Vis
Fluorescence Spectroscopy FL
Turbidity
Scanning Electron Microscopy SEM
Transmission Electron Microscopy (+EDX) TEM
Atomic Force Microscopy AFM
Confocal Microscopy
Field Flow Fractionation FFF
Dynamic Light Scattering DLS
Static Light Scattering SLS
Molecular Gas Adsorption (BET) BET
Dialysis
Electrophoresis and Capillary Electrophoresis
Ultrafiltration
Centrifugation
Filtration
Nanoparticle Tracking Analysis NTA
Size Exclusion Chromatography SEC
Selected Area Electron Diffraction SAED
Zeta Potential by DLS
X-ray Diffraction XRD
Thermogravimetric Analysis TGA
Quartz Microbalances
Differential Scanning Calorimetry DSC
Dynamic Mechanical Analysis DMA
Fourier Transform Infrared Spectroscopy FT-IR
FT-IR Imaging
Raman Spectroscopy
TGA coupled with Gas Chromatography – Mass Spectrometry TGA-GC/MS
Laser Induced Plasma Spectroscopy LIPS
Hydrodynamic Chromatography HDC
Laser Induced Breakdown Detection LIBD
X-ray Photoelectron Spectroscopy XPS
Electron Energy Loss Spectroscopy EELS (+EDX)
Commonly used in the Microscopy
characterization of techniques
nanomaterials
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18. Nanomaterial Characteristics
Size Particle Size Surface Surface Shape Agglomeration Structure Composition
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Distribution Charge Area
Not widely Available from
applicable PerkinElmer
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19. regulations and working with the EPA to establish nanomaterial guidelines for health
and safety for the workers and for the end users. The EPA has declared that nano-
carbon is a new material and use and requires that it be substantiated as safe.37
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So airborne nanoparticles, nanoparticles in water, and skin exposure to nanomaterials
are being addressed by all parties concerned, but there is much research to be done
and a key aspect of this work is the need for methods and analytical techniques that
can separate, identify and quantitate ENPs in amongst naturally occurring nanoparticles.
As consumers, we should to be aware of nanoparticles in the products we use and
the food we eat, but currently there are no labeling regulations. There is legislation
being implemented in Europe that requires cosmetic manufacturers to list any
nanoparticles used in their products.38,39 This is the first European industry to have
required labeling. To date labeling is not required for any other industries anywhere
in the world.
Within the United States, the EPA and other government agencies are proactive in
regards to nanotechnology. The Federal Government has established the National
Nanomaterial Initiative (NNI) where government agencies and private industry meet
to discuss and understand nanomaterial implications of the environment and human
health. PerkinElmer participates in NNI meetings and is working with the EPA and
other agencies to better understand nanomaterials. Figure 8 depicts the life cycle
of nanomaterials in the environment and identifies what government agencies are
addressing these segments of the life cycle. The source and emission in Figure 8
corresponds to the manufacturing waste in figure 7. The waste interaction with
the environment could occur from material taken to a dump, incinerated or washed
down the drain. Environmental Health and Safety (EHS) applies to nanomaterial
workers as human exposure could occur during the manufacturing process.
Figure 8. Nanomaterial life cycle in the environment.
Source: DOE Molecular Foundry – Lawrence Berkeley National Laboratory.
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20. Q What solutions are provided by PerkinElmer for nanomaterials
characterization?
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A Although nanomaterials are small and cannot be seen with the naked eye, it seems likely
that their impact on the world will be huge. PerkinElmer is involved in the nanomaterial
revolution by participating and working with government agencies, research universities,
nanomaterial manufacturers, and end-user industries. While PerkinElmer does not supply
all the possible measurement technologies required as listed in Table 4, in certain important
areas we have a rich solution offering to enable customers to make critical measure-
ments. As customers discover what measurement parameters and performance criteria
are important, we believe that our offerings will deliver more value and come to be
recognized as important solutions to challenging problems.
PerkinElmer has the following solutions available for customers who require
nanomaterial characterization:
Table 5. PerkinElmer analytical solutions.
Analytical
Technology Application
UV/Vis The LAMBDA™ 850/950 are being used to assess nanomaterial surface coating on glass for the solar
energy industry. The LAMBDA 1050 equipped with a 150 mm integrating sphere has been used to
measure the band gap (an important semiconductor characteristic) of TiO2 nanomaterials.40
Fluorescence The LS-55 is being used to measure the fluorescence shift in quantum dots. In addition, quantum dots
are being considered as reference materials to calibrate fluorescence spectrometers.41
FT-IR Photocatylitic degradation of dyes and other photosensitive materials. Use of FT-IR imaging to examine
gold nanostructures embedded in 50 nm thin polymethylmethacrylate film to develop novel materials.40
Raman Surface characterization of films and other substrate materials that are coated with nanomaterials.
TGA Pyris™ 1 TGA finds application in characterizing CNTs during the manufacturing process and for
incoming inspection.
DSC DSC 8500 is being used to characterize amorphous pharmaceuticals that employ nanomaterials such as
determining the glass transition temperature (Tg) to assess the nano-crystalline structure.40 StepScan™
and HyperDSC® have been used to study the rigid amorphous fraction in polymethylmethacrylate silicon
oxide nano-composites.42
DSC-Raman Morphology characterization of SWCNTs in composites.
DMA To assess the strength of different composite mixtures of CNT/epoxy.
TGA-GC/MS Being used by an EPA lab to measure the degree of coating on ENPs under different conditions.
AA Mainly used to measure bulk concentrations in fabricated materials such as Ag nanoparticle impregnated
fabrics [Ag in textile/Germany].
ICP Assessment of gold and copper concentration in digests of elemental nanomaterial suspensions.43
ICP-MS Rapidly becoming the elemental measurement technique of choice for ENPs, especially Au, Ag, Pt, Ce,
W, Ti, etc. in the environment and increasingly being coupled with Field Flow Fractionation. In a recent
review article on this hyphenated technique, of the 28 papers referenced, 18 used PerkinElmer® ICP-MS
systems.31 Researchers are now looking to perform single particle analysis with ICP-MS as this gives
additional size and distribution information.44
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21. PerkinElmer is an active member of the ISO group establishing nanomaterial testing
protocols and participates in NNI meetings and a variety of international nanomaterial
scientific meetings.
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Q Where can I find more information?
A To learn more about PerkinElmer analytical solutions for nanomaterial applications,
please visit http://www.perkinelmer.com/nano. This will continue to develop in the
future to provide access to key scientific publications, background information,
application notes and links to useful websites.
This ‘Primer’ is intended to provide you with useful background information; it
cannot answer every question, but it should stimulate material characterization
discussions that hopefully will lead to an analytical solution.
Have questions, need more information? Please contact Andrew Salamon, Patrick
Courtney or your local PerkinElmer sales representative. We are happy to answer
your nano-related questions.
References
1. Burnett, K., and Tyshenko, M.G., (2010), A comparison of human capital levels
and the future prospect of the nanotechnology industry in early sector investors
and recent emerging markets, Intl. J. of Nanotechnology, 7, 2/3, 187-208. http://
www.inderscience.com/browse/index.php?journalID=54&year=2010&vol=7&issue=2/3
2. American Heritage Dictionary, March 2010. http://dictionary.reference.com/
browse/Nanotechnology
3. International Standards Organization, 2008, ISO/TS 27687:2008 and 2010, ISO/
CD TS 80004-1:2010
4. Klaine, S.J., Alvareez, J.J., Batley, G.E., et al., (2008), Critical Review, Nanomaterials in
the environment: behaviour, fate, bioavailability and effects, Environ. Toxicol. Chem,
27, 1825-1851
5. National Nanomaterial Initiative, March 2010: http://www.nano.gov/Nanotechnology_
BigThingsfromaTinyWorldspread.pdf
6. National Nanomaterial Initiative, March 2010: http://www.nano.gov/html/facts/faqs.html
7. Nature, (2009), 461, 1036-1037, doi: 10.1038/4611036a
8. National Nanomaterials Initiative, 2010, Supplement to the President’s FY2011
budget http://www.nano.gov/NNI_2011_budget_supplement.pdf
15
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22. 9. Gion, A., (2010) Bucky Balls, March 2010: http://www.3rd1000.com/bucky/bucky.htm
10. Evident Technologies, (March 2010): http://www.evidenttech.com/quantum-dots-
explained/how-quantum-dots-work.html
TABLE OF CONTENTS
11. Nanoco Group PLC website, (2010), http://www.nanocotechnologies.com/content/
AboutUs/AboutQuantumDots.aspx
12. Nanocomposix Corp., (March 2010): http://www.nanocomposix.com/product-gold/
nanoxact-gold.html
13. Li, D., Wang, Y., Xia, Y., (2004), Electrospinning Nanofibers as Uniaxially Aligned
Arrays and Layer-by-Layer Stacked Films, Adv. Matls., 16, 4, 361-366, DOI
10.1002/adma.200306226, http://www3.interscience.wiley.com/journal/107630203/
abstract
14. Patel, S., Li, S., (2007), Bioactive Aligned Nanofibers for Nerve Regeneration,
Nanotech Conference, Santa Clara, CA, USA. http://www.nsti.org/BioNano2007/
showabstract.html?absno=1301
15. Hegde, R.R., Dahiya, A., Kamath, M.G., (2005), Nanofiber nonwovens, http://web.
utk.edu/~mse/Textiles/Nanofiber Nonwovens.htm
16. Woodrow Wilson Center for Scholars, Project on Emerging Technologies (2010),
http://www.wilsoncenter.org/index.cfm?topic_id=166192&fuseaction=topics.home
17. Nanoiron Future Technology, Rajhard, Czech Republic, http://www.nanoiron.cz/en/
home-page
18. Moriggi, L., Cannizzo, C., Dumes, E, et al., (2009), Gold Nanoparticles Functionalized
with Gadolinium Chelates as High-Relaxivity MRI Contrast Agents, J. Am. Chem.
Soc., 131 (31), pp 10828–10829, DOI: 10.1021/ja904094t,
19. Nanovations Pty, Ltd., New South Wales, Australia, (2010),
http://www.nanovations.com.au/index.htm
20. Nanocor, USA, www.nanocor.com
21. A to Z of Nanotechnology website, (2010), http://www.azonano.com/details.asp?
ArticleID=1339
22. Yang, W., Peters, J.I., Williams III, R.O., (2010), Inhaled nanoparticles – a current
review., Int. J. of Pharmaceutics, 356, 1-2, 239-247, doi:10.1016/j.ijpharm.2008.
02.011
23. 3XDRY® Essex Fishing Shirt, (2010). http://www.simmsfishing.com/site/3xdry_essex_
shirt.html#
24. PuckSkin Hockey Apparel, BC, Canada, (2010), http://www.puckskin.com/home.htm
16

23. 25. Nanocomp Technologies, Concord, NH; USA, (2010), http://www.nanocomptech.
com/html/nanocomp-what-we-do.html
26. Federal Aviation Administration, Fire Safety Division, Washington DC, USA, (2010),
TABLE OF CONTENTS
http://www.fire.tc.faa.gov/research/targtare.stm
27. Energenics web page, suppliers of Envirox™ http://www.energenics.org/envirox.html
28. Holmenkol AG, Germany, (2010), http://www.nanowax.de/index.php?id=10&L=1
29. Easton Sports Inc., CA, USA, http://eastonbike.com/
30. Goa, F., University of Nottingham Trent, UK, January 26, 2010, Lecture Presentation
31. Dubascoux, S., Le Hecho, I., Hassellöv, M., et al, (2010), Field-flow fractionation
and inductively coupled plasma mass spectrometer coupling: History, development
and applications. J. Anal. Atom. Spectrom, DOI: 10.1039/b927500b, web
prepublication 23-March-2010
32. Postnova Corp., Germany, (2010), http://www.postnova.com/
33. Wyatt Technology Corporation,USA, (2010), http://www.wyatt.com/
34. Mansfield,E., Kar, A, Hooker, S.A., (2010), Applications of TGA in quality control
of SWCNTs, Anal. Bioanal. Chem., 396(3), 1071-1077.
35. Sahle-Demesie, E., EPA, USA, (March 2010), Personal communication with A. Salamon,
PerkinElmer
36. National Nanotechnology Initiative - Human Health Workshop (2009), Washington
DC., USA, November 17 – 18.
37. Environmental Protection Agency, Washington DC, USA, (2010), Control of nanoscale
materials under the Toxic Substances Control Act, http://www.epa.gov/oppt/nano/
38. European Union Cosmetics directive, 76/768/EEC, 25 March 2009
39. Bowman, D.M., van Calster, G., Friedrichs, S., (2010), Nanomaterials and regulation
of cosmetics, Nature Nanotechnology 5, 92 doi:10.1038/nnano.2010.12
40. Courtney, P., (2009), Functional measurements in nanomaterisals using optical
and thermal techniques, PerkinElmer poster presented at the 3rd Nanomaterials
Conference, Bonn, Germany, 16 – 18 June. http://www.nanotechia.org/events/
nanomaterials-2009
41. Upstone, S., Seer Green, UK, (2008), PerkinElmer Presentation, Colloquium on
Optical Spectroscopy (COSP), Berlin, Germany
42. Schick, C., (2009), Study Rigid Amorphous Fraction in Polymer Nano-Composites
by Step Scan and Hyper DSC, PerkinElmer Application Note #008648_01
43. Sarojam, P., (2010), Elemental characterization of gold and copper nanoparticles
with ICP-OES, PerkinElmer Application Note (in preparation)
17
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24. 44. Heithmar, E.M., and Siska, E.M., (2010), Single particle-inductively coupled plasma
mass spectrometry of metal-containing nanomaterial in surface waters around Las
Vegas, Nevada, USA, Poster presentation at the 2010 Winter Conference on
TABLE OF CONTENTS
Plasma Spectrochemistry, Fort Myers, Florida, USA, January 4-9.
Useful books and websites for more information
Nanochemistry – A Chemical Approach to Nanomaterials, 2nd Edition, (2009), Ozin,
G.A., Arsenault, A.C., Cademartiri, L.,RSC Publishing, Cambridge, UK, ISBN: 978-1-
84755-895-4
Introduction to Nanoscience, (2010), Lindsay, S.M., Oxford University Press, Oxford,
UK, ISBN: 978-019-954420-2
PerkinElmer Nano Applications Library, http://www.perkinelmer.com/nano
U.S. National Nanomaterials Initiative (NNI), http://www.nano.gov/
University of California Center for Environmental Implications of Nanomaterials, USA,
http://cein.cnsi.ucla.edu/pages/
Duke University Center for the Environmental Implications of Nanotechnology, USA,
http://www.ceint.duke.edu/
U.S. Department of Defense, Nano-Funding, http://nanosra.nrl.navy.mil/funding.php
Current Government Nanomaterial Solicitations, http://www.nano.gov/html/funding/
currentsol.html
Nanotechnology Nanomaterial Suppliers, http://www.nanowerk.com/nanotechnology/
nanomaterial/suppliers_plist.php?subcat1=np
Overview of ground water treatment and chemistry with nano zerovalent iron,
http://cgr.ebs.ogi.edu/iron/
UK-based nanotechnology forum intended for anyone who wants to learn more about
this technology, products etc., http://www.nanoandme.org/home/
Nanotechnology Now information forum, http://www.nanotech-now.com/nano_intro.htm
A to Z Nanotechnology, a free-to-access nanotechnology website, http://www.azonano.
com/default.asp
Nanotechnologies Industry Association, Brussles, Belgium, (2010), http://www.nanotechia.
org/content/aboutus/
The Nanotube Site. Very comprehensive listing of information and publications on
carbon nanotubes. (2010). http://www.pa.msu.edu/cmp/csc/nanotube.html
18

25. TABLE OF CONTENTS
Looking for other ways to learn more about Nanotechnology?
There are many different resources available that allow scientists to
explore the depths of the Nanotechnology world.
Please see below for some recommended online resources:
LinkedIN Groups:
• Nanotechnology in Drug Delivery
• Nanotechnology Zone
• Nanotechnology : Materials and Fabrication
Websites
• Nano.gov
• http://sis.nlm.nih.gov
• www.perkinelmer.com/nano
?

26. White
Nanopharmaceuticals
TABLE OF CONTENTS
paper
Nanomaterials
Author
Andrew W. Salamon
Sr. Staff Scientist
PerkinElmer, Inc.
Shelton, CT USA
This poster compares the nano-region to things we know, such as a pin, insect and cells to provide a visual perspective.
PerkinElmer, Inc.
Nanotechnology is the science and technology of precisely manipulating the structure of matter at the molecular level. 940 Winter Street
For Nanomaterial Applications, please visit www.perkinelmer.com/nano Waltham, MA 02451
Copyright ©2010, PerkinElmer, Inc. All rights reserved. PerkinElmer is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners. 009227_01
Nanopharmaceuticals “Nanotechnology is widely anticipated as one of the key
Introduction
and PerkinElmer technologies of the 21st century.”1 PerkinElmer supplies
nanomaterial characterization instruments for industrial and
academic nanotechnology research. Industrial nanotechnology
applications are far-reaching, spanning all science and engineering disciplines. One of the most
promising nanotechnology fields is Nanopharmaceuticals. Because nanomaterials may enter the
body through dermal exposure, inhalation, ingestion, or ocular contact, they lend themselves to
innovative drug delivery systems. Pharmaceutical research, toxicology studies, formulation, and
manufacture of pharmaceutical products require material characterization to ensure consistent drug
safety and effectiveness. PerkinElmer has been providing analytical instruments to the pharmaceutical
industry for more than 60 years. As such, nanopharmaceutical material applications are no exception for
PerkinElmer.
What are Nanomaterials?
Nanomaterials are materials that range in size from approximately 1 nm to 100 nm. There are more
rigorous definitions that are specific to certain applications such as cosmetics. In Europe’s efforts to
label cosmetics that contain nanoparticles, this definition evolved: “nanomaterial means an insoluble
or biopersistant and intentionally manufactured material with one or more external dimensions, or
an internal structure, on the scale from 1 to 100 nm.”2

27. Engineered nanoparticles are of great scientific interest. What material parameters are important?
They effectively bridge a gap between bulk materials and To completely characterize nanomaterial it is necessary to
atomic and molecular structures. Nanoparticle mechanical know a multitude of chemical and physical pararmeters
TABLE OF CONTENTS
properties are different than bulk material. Surface area including: the size of the particle, their shape, surface
is disproportionate to weight, for instance, an 8 nm gold characteristics, the presence of surface coatings, and the
material has a surface area of 32 square meters per gram. presence of impurities.
Materials of nanoscale proportions exhibit unique
characteristics. Examples are gold nanopartilces and silver Consequently, at the nanoscale, analytical measurement
nanoparticles smaller than 12 nm that exhibit an affinity for challenges are considerable and the ability to use, for
magnetism. In bulk form gold and silver are non-magnetic. example, one technique such as inductively coupled plasma
and mass spectrometry (ICP-MS) to measure the elemental
There is a diverse field of applications over a broad range of concentration of gold in a suspension as the only metric,
industries: does not provide enough information.
• Energy, energy-conservation, pharmaceuticals, chemicals,
catalysts How are engineered nanomaterials measured?
• High performance-composite engineered materials – Seven of the nine nanomaterial characteristics:
military to leisure time applications Particle Size, Size Distribution, Surface Charge,
• Coatings, electronics, sensors and displays Surface Area, Shape, Agglomeration, and Structure,
• And more are characterized by one of the following analytical
techniques:
What materials are used to make Engineered • Scanning Electron Microscopy (SEM)
Nanomaterials? • Transmission Electron Microscopy (TEM)
There are several categories of nanomaterials, naturally • Atomic Force Microscopy (AFM)
occurring nanomaterials are found in nature, engineered • Confocal Microscopy (CFM)
nanomaterials are synthesized for a specific purpose or
• Dynamic Light Scattering (DLS)
function, manufactured nanomaterials are produced for
• Field Flow Fractionation (FFF)
commercial purposes, and incidental nanomaterials are
generated as an unintentional by-product of a process.3 • Molecular Gas Adsorption (BET)
• Electrophoresis Particle Size
Some engineered nanomaterials are:
• Gold, Silver, Copper, Selenium, Iron, Titanium, Zinc, and Note
Aluminum
Ultraviolet/Visible Spectroscopy and Fluorescence
• Zinc oxide, Titanium oxide Spectroscopy are used for particle size identification as long
• Carbon – Carbon Nanotubes, Buckyballs, and Graphene. as the material is known and it is reflective. Fluorescence
• Clay Spectroscopy is also used for agglomeration studies.
• Organic materials/biodegradable
Nanoparticle Concentration and Composition are two nano-
particle characteristics that that are not covered by the
analytical techniques described in the paragraph above.
There are many analytical techniques that do cover concen-
tration and composition. The correct analytical technique is
determined by the material, coatings, and nano application.
For Nanoparticle Concentration you might choose one or
several of the following analytical techniques:
• Inductively Coupled Plasma and Mass Spectroscopy
(ICP-MS)
• Liquid Chromatography and Mass Spectroscopy (LC-MS)
• Ultraviolet/Visible Spectroscopy (UV/Vis)
• Fluorescence Spectroscopy (FL)
Key parameters to characterize nanomaterials.
Figure adopted from Hassellöv, M., and Kaegi, R., Analysis and
characterisation of manufactured nanoparticles in aquatic environments,
Chapter 6 in Environmental & Human Health Impacts of Nanotechnology,
Eds., Lead, J.R. & Smith, E., 2009 Blackwell Publishing Ltd.
2
?

28. For Nanoparticle Composition you might choose one of the Who is involved in Nanopharmaceuticals?
following analytical techniques: all major pharmaceutical companies are involved in
• Inductively Coupled Plasma and Mass Spectroscopy (ICP-MS) Nanopharmaceuticals.
TABLE OF CONTENTS
• Liquid Chromatography and Mass Spectroscopy (LC-MS) • GlaxoSmithKline (GSK)
• Ultraviolet/Visible Spectroscopy (UV/Vis) • Merck
• Fluorescence Spectroscopy (FL) • Johnson & Johnson
• Thermogravimetry (TGA) • Novartis
• Differential Scanning Calorimetry (DSC) • Pfizer
• Dynamic Mechanical Analysis (DMA) Small “start-up” nanopharmaceutical companies play an
• Fourier Transform Infrared Spectroscopy (FT-IR) important role in research and development. Some not-so-
well-known, small, new, nanopharmaceutical-focused
• Raman Spectroscopy
companies are:
• Thermogravimetry, Gas Chromatography, and Mass
• Cerulean Pharma Inc.
Spectroscopy (TGA-GC/MS)
• Bind Biosciences
• Thermogravimetry and Mass Spectroscopy (TGA-MS)
• Selecta Biosciences
For composition, you may be concerned with purity or the
coatings on nanomaterials besides the substrate material of all U.S. universities that conduct pharmaceutical or medi-
the nanoparticle. All of the italicized analytical techniques cal research are involved in nanopharmaceuticals. Some of
are nano-characterization instruments that PerkinElmer the most well known academic nano-research institutions
offers. Please remember that there is not just one analytical are:
technique that can characterize a nanomaterial. All analytical
techniques are also listed in Table 1. • UCLA
• Rice University
What pharmaceutical applications are likely to • Georgia Tech
utilize nanomaterials?
• MIT
Nanopharmaceutical markets include products for humans,
pets, and Farm animals. From the list below you can see • Yale University
that nanotechnology innovation will affect most people: • Many more…
• Medicines for most diseases and illnesses – tablet or
academic authors of nanopharmaceutical scientific
liquid form
research papers span the globe. They originate from:
• Vaccines for most diseases and illnesses
• Chemotherapeutic agents • Iran
• Anti-cancer drugs • Israel
• Personal care products: shampoos and body washes, etc. • Poland
• Medical devices and diagnostics, Molecular diagnostics,
• Italy
Diagnostic tests
• Germany
• Dental health products
• Over-the-counter medicines • Russia
• Nutritional products • China
• Managing-obesity products • Australia
• Medical and Surgical devices • Japan
• Ocular health products and instruments
• UK
• Cardiology and Pulmonary medicine
• Many more…
• Osteoporosis
• Injury healing
• Generic pharmaceuticals
• Smoking cessation
3

29. Table 1. Nanomaterial characteristics and applicable analytical technologies.
Na
TABLE OF CONTENTS
Concentration Particle Size Particle Size
Analytical Technique Distribution
Inductively Coupled Plasma – Mass Spectrometry ICP-MS
Field-flow Fractionation + ICP-MS FFF-ICP-MS
Liquid Chromatography – Mass Spectrometry LC-MS
Optical Spectroscopy – UV/Vis UV/Vis
Fluorescence Spectroscopy FL
Turbidity
Scanning Electron Microscopy SEM
Transmission Electron Microscopy (+EDX) TEM
Atomic Force Microscopy AFM
Confocal Microscopy
Field Flow Fractionation FFF
Dynamic Light Scattering DLS
Static Light Scattering SLS
Molecular Gas Adsorption (BET) BET
Dialysis
Electrophoresis and Capillary Electrophoresis
Ultrafiltration
Centrifugation
Filtration
Nanoparticle Tracking Analysis NTA
Size Exclusion Chromatography SEC
Selected Area Electron Diffraction SAED
Zeta Potential by DLS
X-ray Diffraction XRD
Thermogravimetric Analysis TGA
Quartz Microbalances
Differential Scanning Calorimetry DSC
Dynamic Mechanical Analysis DMA
Fourier Transform Infrared Spectroscopy FT-IR
FT-IR Imaging
Raman Spectroscopy
TGA coupled with Gas Chromatography – Mass Spectrometry TGA-GC/MS
Laser Induced Plasma Spectroscopy LIPS
Hydrodynamic Chromatography HDC
Laser Induced Breakdown Detection LIBD
X-ray Photoelectron Spectroscopy XPS
Electron Energy Loss Spectroscopy EELS (+EDX)
Commonly used in the Microscopy
characterization of nanomaterials techniques
4
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30. Nanomaterial Characteristics
Size Particle Size Surface Surface Shape Agglomeration Structure Composition
TABLE OF CONTENTS
Distribution Charge Area
Not widely Available from
applicable PerkinElmer
5

31. What are nanomaterials used for in Selecta’s unique tSVP™ platform includes a self-assembling
pharmaceuticals? nanoparticle platform that is synthetic, modular, and engi-
Nanomaterials are used primarily for drug delivery systems, neered for highly-effective targeting to immune cells. The
TABLE OF CONTENTS
but also are used for product packaging, colorants; bone, tSVP™ vaccines incorporate only the essential elements
skin, and muscular growth; and medical imaging. required for a specific, robust immune response, based on
precise engineering that is only possible with Selecta’s
Drug delivery systems can be simple such as gold nano- proprietary, nanoparticle self-assembly process.
particles coated with a vitamin or nutrient. Or it could be
as complex as a nanoparticle that is coated with functional Below is a diagram of a product from Bind Biosciences
groups that target specific tumor cells or organs and then inc. that describes another type of complex nano-
are able to release the drug in some manner; time-released, pharmaceutical delivery system.6
released by heat, released by light, or released by magnetism.
There are even nano-delivery systems that seek and destroy Targeted Nanoparticle Platform
cells by entering the targeted cells and explode. Thus BIND’s targeted nanoparticles consist of the following
exploding within the cell and completely destroying the cell. components that facilitate optimization and control:
Some time-released nanopharmaceuticals are encapsulated
in lipids for use in salves and ointments. Titanium Oxide
nanoparticles are used for white colorant in some salves
and ointments and also in Dental Health products.
Below is a diagram of a product from Selecta Biosciences
Company. this complex nanopharmaceutical delivery
system is designed to combat an influenza virus.5
tSVp™ – a new class of synthetic vaccines for Optimal
immune response
Selecta’s targeted Synthetic Vaccine Particle (tSVP™) product
platform enables, for the first time, the highly-precise and
modular development of therapeutic and prophylactic targeting ligand provides recognition, enabling targeted
vaccines with optimal efficacy, duration of coverage and nanoparticles to identify and bind to their intended target
safety, to greatly improve the lives of patients. site. They are designed to recognize specific proteins or
receptors that are found on the surface of cells involved in
Selecta’s tSVP™ platform creates fully-integrated synthetic disease or the surrounding extracellular matrix.
nanoparticle vaccines engineered to mimic the properties
of natural pathogens to elicit a maximal immune response. Surface functionalization shields targeted nanoparticles
The tSVP™ vaccines are rationally designed to optimize the from immune surveillance, while providing attachment for
presentation of antigens to the nexus of the immune system the targeting ligand through proprietary linkage strategies.
and ensure a focused and undistracted response. Selecta’s We have developed proprietary methods for precisely
tSVP™ platform accomplishes this by delivering antigens controlling the surface characteristics necessary to ensure
and adjuvants, within the same biodegradable nanoparticle, the drug is delivered efficiently and consistently.
directly to antigen-presenting cells. This approach maximizes
polymer matrix encapsulates payload molecules in a matrix
the immune response while minimizing undesirable off-
of clinically validated biodegradable and biocompatible
target effects.
polymers that can be designed to provide the desired drug
release profile.
therapeutic payloads can be incorporated into our
targeted nanoparticles, including small molecules, peptides,
proteins and nucleic acids, such as siRNA.
6
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32. Below is a diagram from Cerulean pharma inc. that des- who had previously relapsed and progressed on multiple
cribes a complex nanopharmaceutical delivery system. lines of prior therapy. Notably, these advanced cancer
patients had highly aggressive tumor types, such as non-
TABLE OF CONTENTS
CRLX101 small cell lung and pancreatic cancer, with typical survival
of less than six to eight months. These observations corre-
CRLX101 is comprised of the high potency anti-tumor agent
late with CRLX101’s pharmacokinetics profile including an
camptothecin coupled to a cyclodextrin based polymer that
extended half-life of more than 30 hours and a low volume
self-assembles into nanoparticles of consistent size and
of distribution of 2.1 liters per square meter, an indication
other physical attributes.
of low systemic exposure of free drug. These data are also
Below is a schematic representation of CRLX101. consistent with animal pharmacokinetic data demonstrating
a high and prolonged localized drug exposure in the tumor.
camptothecin
(CPT)
Cerulean Senior Director of Research Scott Eliasof, Ph.D.,
polyethylene
glycol (PEG) presented recent results on the Company’s pre-clinical lead
b-cyclodextrin
candidate, CRLX288, a docetaxel nanopharmaceutical. His
(CCD)
presentation focused on animal studies showing a significant
improvement in the therapeutic index of CRLX288 compared
to the parent drug docetaxel. Specifically, Dr. Eliasof reported
that CRLX288 achieved complete regression and inhibition
CRLX101 provides clinical validation of the CDP technology of tumor growth in 100 percent of the animals studied for
improving the tolerability of the parent drug camptothecin. greater than 100 days post-treatment, at dose levels that
Results from the Phase 1 clinical study of CRLX101 have were well tolerated, in both typical size xenograft tumors
shown that it has a favorable safety profile in patients with of 100 mm3 as well as in xenograft tumors as large as
advanced cancer. Combining camptothecin’s potency and 800 mm3. CRLX288’s superior efficacy over the parent drug
Cerulean’s nanopharmaceutical design features, we believe docetaxel in animal studies was consistent with other pre-
CRLX101 has the potential to kill tumor cells while minimizing clinical findings showing 20 times more drug accumulating
the side effects typically associated with chemotherapy in the tumor as compared to treatment with free docetaxel
treatment. [bulk material].
It is easily noted that all three nanopharmaceutical delivery Together, the Phase 1 findings for CRLX101 and the
systems are very different and all require material character- pre-clinical data on CRLX288 demonstrate that Cerulean’s
ization by some analytical technique. This ensures patient nanopharmaceutical platform has the potential to markedly
safety and product effectiveness for each. enhance efficacy and tolerability of therapeutic agents in
humans. Such biological outcome is targeted to be achieved
Amazing results with drug-containing nanoparticles that are designed to
remain intact in circulation, accumulate in tumor tissues,
When nanopharmaceutical drug delivery systems as sophisti-
enter cancer cells, and provide a long and sustained drug
cated as the three above are used in certain cancer cases the
effect with slow and controlled drug release.
results have been better than traditional bulk chemotherapy
with little or no side effects. Please note that CLRX101 delivers the drug, camptothecin.
Camptothecin is very potent and when delivered in bulk
Below are excerpts from Cerulean Pharma Inc. clinical and
form not only killed the tumors but in some cases killed
pre-clinical Nanopharmaceutical data for their product
patients. When the same dosage of camptothecin is deliv-
CRLX101 and progress with pre-clinical lead CRLX288.
ered in nanoscale increments the drug is still as effective as
Cerulean Chief Medical Officer John Ryan, Ph.D., M.D., in bulk delivery, but there are no side effects. This maybe a
reported results from the dose-finding, safety and tolerability result of attacking the tumor on a cell by cell basis. In fact,
Phase 1 clinical study of CRLX101. Specifically, Dr. Ryan in laboratory tests a double dose of camptothecin bulk form
discussed data establishing the maximum tolerated dose and was delivered on the nano scale and there were still no side
the recommended dose and schedule for a planned Phase 2 effects.9
study. He reviewed observations of progression-free disease
of greater than six months in five advanced cancer patients
7

33. Conclusion European Commission Joint Research Center (JRC), 2010.
PerkinElmer diligently works at being a global leader in
3. International Standards Organization (ISO), Tech Spec
nanotechnology characterization. PerkinElmer participates
ISO/TS80004-1 Nanotechnologies – Vocabulary Part 1:
TABLE OF CONTENTS
in Nano seminars worldwide. PerkinElmer is a member of
Core Terms.
the U.S. Technical Advisory Group (TAG 229) within the
International Standards Organization (ISO). This member- 4. Hasselhov, M., Kaegl, R., “Analysis and Characterization
ship involves writing and reviewing ISO Nanotechnology of Manufactured Nanomaterials in Aquatic
documents for industry, including nanopharmaceuticals and Environment,” Chapter 6 of Environmental and Human
toxicology applications. PerkinElmer also participates in the Health Impacts of Nanomaterials, Eds. Lead, J. and
U.S. National Nanotechnology Initiative (NNI) which helps Smith, E,. Blackwell Publishing Ltd.
set U.S. strategic direction for nanotechnology. PerkinElmer
is a leader in material characterization and with its strength 5. Selecta Biosciences, 2011, Accessed Jan 2011, http://
in characterizing nanomaterials it is very well positioned as a www.selectabio.com/product-platform/index.cfm
leader in nanopharmaceuticals. These are truly exciting times
6. Bind Biosciences, Inc. 2010, Accessed Jan 2011, http://
in nanoscience.
www.bindbio.com/content/pages/technology/index.jsp
Additional Readings and websites 7. Cerulean Pharma Inc. Clinical Trials, Accessed Jan 2011,
• Nanotechnology and Engineering Nanoparticles – http://www.ceruleanrx.com/clinical_trials.html
A Primer.
8. Cerulean Pharma Inc. Press release, Nov 2010,
• Nanopharmaceutical Applications Library accessed Jan 2011, http://www.ceruleanrx.com/Press/
Both suggested readings above are found CeruleanPressRelease_120910.pdf
www.perkinelmer.com/nano
9. Glucksmann, A., Cerulean Pharma Inc., Dr. Clucksmann’s
• U.S. National Nanomaterials Initiative (NNI), http://www. presentation at the NNI Summit meeting, Washington,
nano.gov/ DC, Dec 10, 2010.
• University of California Center for Environmental
10. Cerulean Pharma Inc., Press release, Cerulean
Implications of Nanomaterials, USA, http://cein.cnsi.ucla.
Pharma Inc. Senior Executive to Present at the
edu/pages/
National Nanotechnology Innovation Summit,
• International Standards Organization, http://www.iso.org/ Dec 9, 2010, http://www.ceruleanrx.com/Press/
iso/home.htm CeruleanPressRelease_120910.pdf
References 11. Salamon, A.W. and et al, PerkinElmer, 2010,
Nanotechnology and Engineering Nanoparticles –
1. Novartis Pharmaceuticals Corp. 2006, accessed Jan
A Primer.
2011, http://www.corporatecitizenship.novartis.com/
downloads/business-conduct/Nanotechnology_Based_ 12. PerkinElmer Nanomaterials website, Nanopharmaceutical
Medicines_External_Position.pdf Applications Library, www.perkinelmer.com/nano
2. Lövestam, G., Rauscher, H. et al, Considerations on a
Definition of Nanomaterial for Regulatory Purposes,
PerkinElmer, Inc.
940 Winter Street
Waltham, MA 02451 USA
P: (800) 762-4000 or
(+1) 203-925-4602
www.perkinelmer.com
For a complete listing of our global offices, visit www.perkinelmer.com/ContactUs
Copyright ©2011, PerkinElmer, Inc. All rights reserved. PerkinElmer® is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners.
009561_01
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34. TABLE OF CONTENTS
Thermal Analysis
• Improved HyperDSC Method to Determine Specific Heat Capacity of
Nanocomposites and Probe for High-Temperature Devitrification
• A Study of Aged Carbon Nanotubes by Thermogravimetirc Analysis