harvard-niehs center overview: cores and activities · p-c-m properties can be modified (primary...
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Harvard-NIEHS Center overview:
Cores and ActivitiesPhilip Demokritou, Center Director
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Collaborating Institutions
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Our Center builds upon the infrastructure and interdisciplinary experience of
five existing academic research centers/Institutes in the fields of
nanomaterial synthesis, characterization, nanobiology and nanotoxicology
research:
• Center for Nanotechnology and Nanotoxicology at Harvard School of
Public Health; (Dr Demokritou)
• Center for Nanoscale Systems (CNS) at Harvard School of Engineering
and Applied Sciences; (Dr Bell)
• Laboratory for Advanced Carbon-based Nanomaterials at MIT; (Dr
Strano)
• Particle Engineering Research Center (PERC) at University of Florida; (Dr
Moudgil)
• Forest Bio-products Research Institute at University of Maine. (Dr
Bousfield)
Our mission statement
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We will work across disciplines, share new ideas, develop industry-
relevant reference ENMs, and work with the nanotox consortium to
develop multidisciplinary projects and methods to advance ourunderstanding on nano-safety.
• Where Applications of Engineered Nanomaterials and
Nanotechnology meet Nanosafety research– Vision: Integrate material & exposure science and nanotoxicology risk assessment
to pave the way towards sustainable nanotechnology
– Research Areas: Environmental nanotechnology, safer by design synthesis of ENMs, exposure science, inhalation and cellular toxicology, life cycle implications
of nano-enabled products and development of novel methods for the physico-
chemical and toxicological characterization of nanomaterials
– Mission: Bring together ALL stakeholders: industry, academia, policy makers and the general public for sustainable development of NT industry
– Industrial Partners: Over 20 partners ( BASF, Panasonic, Nanoterra, STERIS, AVECTAS , etc)
– International in nature: Extensive network of collaborators including US Federal Agencies, and Universities around the world (ETH Zurich, NTU- Singapore, RIVM,
MIT, SUNY, UMass, Northeastern Univ., NIOSH, CPSC, etc)
Website: http://hsph.harvard.edu/nano
Harvard Center For Nanotechnology and Nanotoxicology
(2015-2016)
Back Row (left to right): Ya Gao, Georgios Pyrgiotakis, Thomas Donaghey, Ramon
Molina, Glen Deloid, Phil Demokritou, Dilpreet Singh, Joe Brain, Akira Tsuda, Edgar
Diaz, Jin-Ah Park, Yanli wang and Xunzhi Zhu
Sitting (from left to right): Caroline Cirenza, Sylvia Rodrigues, Archana
Vasanthakumar, Sandra Pirela, Christa Watson, Jiayuan Zhao, Jenifer Mitchel,
Guanghe Wang.
ENM Synthesis Core
Metals /Metal Oxides (FSP): P. Demokritou
Metals/Metal Oxides (Wet synthesis): B. Moudgil
Carbon based ENMs (Graphene, CNTs, etc): M. Strano
Nanocellulose: D. Bousfield
ENM SYNTHESIS USING FLAME SPRAY
PYROLYSIS (AEROSOL REACTORS)
Philip Demokritou, Harvard University
Flame Spray Pyrolysis Synthesis: Principle of operation
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“Bottom up” approach for Me/MeOsynthesis
Industry relevant method A liquid precursor which contains the
solution of an organo-metal is pumped though a nozzle.
Fine droplets are formed and dispersed using O2.
Droplets are ignited using a small CH4 flamelet
Primary Particles are formed by “homogenous nucleation”
Larger size aggregates and agglomerates are subsequently formed .
Particle formation and properties can easily be controlled by adjusting the flame conditions.
Versatile Engineered Nanomaterial Generation System (VENGES)
Features:
A Platform for pcm characterization & in-vitro , in-vivo tox studies
Based on industry relevant, flame spray pyrolysis (FSP) aerosol reactors
Versatile: All Me and MeO can be synthesized
P-c-m properties can be modified (primary particle and aggregate sizes, crystalinity, shape, etc).
ENMs are produced continuously in the gas phase allowing to transfer them with controlled agglomeration to inhalation chambers.
T1
QD
FMPS P-TRAKCO2, CO,
RH, T2NO2BUFFER
QPQAQR
ENM sampling/
collection
liquid
precursor
CH4/O2
support
flame
O2
dispersion
QS
50
cm
HEPA
HE
PA
HE
PA
filter
Animal exposure
chamber
Flame Synthesis Animal Exposure
System
Exposure Monitoring Equipment
(Demokritou et al., Inh Tox. 2010)
Sampling
Synthesis
Exposure
(1) Demokritou et al. Inh. Toxicology, 2010 (2) Gass et al. Sus. Che. & Eng, 2012
Coating Reactor during Synthesis
Particle Collection Filter
In flight SiO2 coating of ENMs using the Harvard VENGES:
Core-shell ENMs
(1) Sotiriou et al., Curr Opin Chem Eng 2011, 1, 3 – 10(2) Xia et al., ACS Nano 2011, 5, 1223 – 1235 (3) Gass et al. Sus Chem and Eng, 2013, 7,39(4) Teleki et al., Chem. Mater. 2009, 21, 2094–2100(5) Sotiriou et al., Adv. Funct. Mater. 2010, 20, 4250–4257
Tox. Pathways for Me and MeOx
Scalability?
• Reduce Toxicological footprint• Maintain functional properties of ENMs
(optoelectronic, mechanical, etc)• Scalability is the big challenge
Elements of a Safer by Design Approach
A Safer by Design Concept for flame-generated ENMs
ZnO Case Study: “Safer by design” cosmo-ceutical products
• The Yan: ZnO Nanorodscan block effectively UV while remain transparent to visible light1
• The Yin: ZnO release ions and is photocatalyticallyactive -> ROS generation-> Genotoxic2
1. Sotiriou et al. ES:Nano, 20142. Watson et al. ACS Nano, 2014
SYNTHESIS OF METAL AND METAL OXIDES USING
HIGH PRECISION & THROUGHPUT HYDROTHERMAL
REACTORS (WET CHEMISTRY)
Brij Moudgil, University of Florida
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• Most of the proposed particulate systems related research activities at the University of Florida will be conducted at the Particle Engineering Research Center (PERC). PERC has a dedicated 25,000 ft2 facility (Particle Science & Technology Building) and 17,000 ft2 of laboratory space for the characterization and synthesis of particulate systems.
• Techniques are available for physical, mechanical and chemical analysis of particle systems including size, shape, surface area and porosity, surface chemistry, rheology, tribology, interfacial phenomena, powder mechanics, powder flow and segregation.
• Processing facilities are provided in a 5000 ft2 high-bay pilot plant and including crystallization, classification, size reduction, spray drying, coating, filtration and a wide variety of other techniques. Particle synthesis techniques include a 20 L stirred reactor, spray dryer, fluid bed dryer, wet and dry coating techniques, laser deposition and mechanofusion.
Facilities and Equipment at the University of Florida
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• The PERC works closely with the Major Analytical Instrumentation Center (MAIC), the Interdisciplinary Center for Biotechnology Research (ICBR), and the Center for Environmental & Human Toxicology and has access to their facilities and equipment. MAIC specializes in materials characterization with a variety of state of the art methods such as high resolution scanning and transmission electron microscopy, x-ray photoelectron spectroscopy, and other techniques. See http://www.maic.mse.ufl.edu for a full list of capabilities.
• The ICBR provides state-of-the-art facilities for biological sample analysis ranging from transmission electron microscopy of biological samples to tandem mass spectrometry to gene chip analysis. See http://www.biotech.ufl.edu for a full list of capabilities.
• The Center for Environmental & Human Toxicology is working closely with the PERC to resolve issues in nanoparticle toxicity (see http://www.nanotoxicology.ufl.edu) and has expertise in performing and interpreting in vitro and in vivo toxicity studies.
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• Image Pro v4.5 Optical Analysis Software, Paar Physica UDS 200 Rheometer, Optical Microscopes, Coulter LS 13320 Particle Size Analyzer, Colloidal Dynamics Acoustosizer, Brookhaven ZetaPlus, Microtrac Nanotrac. For a full listing of capabilities, see https://rsc.aux.eng.ufl.edu/resources/default.asp?s=PAIC.
• The center researchers also have access to facilities at Columbia University (NSF I/UCRC Partner with UF) including atomic force microscope (AFM), quartz crystal microgravimatry (QCM), surface plasmon resonance spectroscope (SPR), Fourier Transform Infrared (FTIR) spectrophotometer, fluorescence spectrophotometer, microcalorimeter, surface area analyzer, scanning electron microscope - energy dispersive x-ray fluorescence (SEM-EDX), inductively coupled plasma (ICP) spectrophotometer, UV/visible spectrometer, particle size analyzer, High performance liquid chromatograph (HPLC/GPC), electron spin resonance spectrometer (ESR), Brookhaven photon correlation spectroscopy (PSC), analytical ultra-centrifuge, dynamic laser scattering equipment, zeta meters.
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Metal and Metal Oxide Materials
NPs Method Size Shape
Au reduction of salts in
aqueous conditions 1-100 nm
spheres, rods,
other shapes
possible
Ag
polyol method
< 50 nm spheresreduction of salts in
aqueous conditions
Co chemical reduction in
flow reactor10-100 nm spheres
Fe thermal decom-
position <100 nm spheres, rods
Alsonochemical thermal
decomposition 10-100 nm spheres
Mn chemical reduction 10-100 nm spheres
Znvacuum evaporation
& Condensation10-160 nm
hexagonal
prisms
SiO2
Stober synthesis
5 nm-1 μm spheres, rods,
needlessurfactant-templated
synthesis
Capabilities/Expertise Relevant to HSPS-NIEHS Project
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Production of Core Materials• Most inert metals (Au, Ag, etc.) and oxides (Silica, etc.)
produced in aqueous or water miscible media by chemical reduction.
• Reactive metals (Fe, Al, etc.) produced using organic or vacuum synthesis methods.
• Flow reactor for high precision high throughput.
Silica Spheres
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Flow Reactor: Continuous Production of ENMs
1. Reagent supply pumps2. Reactor 3. Heat exchanger4. Backpressure regulator5. Online characterization6. Collection7. Control hardware and software
• Continuous feedback control and online characterization precisely control reaction conditions and product particle properties.
• Current system capacity is 30mL/min of product suspension.
• Work underway to increase reactor throughput to 300mL/min within the next year.
• The scaled reactor system will also have inline surface modification capabilities (initially gold and silver), permitting one step controlled production of surface modified/core-shell particles.
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Surface Chemistry
• Core inert metal particles electrostatically stabilized (citrate frequently used).
• Reactive metals and some coinage metals have a surface oxide layer.
• Anisotropic particles and certain spherical particles use more strongly interacting compounds (ex. templating surfactants)
• Coinage metals easily modified using sulfur compounds, metal oxides via carboxylates and silicon alkoxides
GRAPHENE, GRAPHENE OXIDE
AND CARBON NANOTUBES
Michael Strano, Massachusetts Institute of Technology
Current Research Areas of Interest
• Energy Generation using Nanomaterials
• Exciton Engineering with Nanoconduits
• Molecular Transport through Nanopores
• Corona Phase Molecular Recognition (CoPhMoRe)
• Plant Nanobionics
• Synthesis and Fabrication of New Materials
Strano Research Group
New to the team (arriving January 2017)
Colloidal graphene and graphene oxide expert
Year 1 Focus: Graphene Production Methods
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NPs Method Size Shape
Graphene oxide Hummer's method (1-4) 1-100 nm Sheet
reduced graphene oxide Solvothermal reduction (3, 5) <100nm Sheet
Mono-layer pristine
graphene solutions
colloidal production,
dispersion and purification
(2, 3, 5)
10 nm- 100
nmSheet
Bi-layer pristine
graphene solutions
colloidal production,
dispersion and purification
(2, 3, 5)
10 nm- 100
nmSheet
Tri-layer pristine
graphene solutions
colloidal production,
dispersion and purification
(2, 5)
10 nm- 100
nmSheet
1. Hummers WS, Offeman RE. Journal of the American Chemical Society. 1958. 2. Jin Z et al. Nat Commun. 2013.
3. Shih C-J, Wang QH, Son Y, Jin Z, Blankschtein D, Strano MS. ACS Nano. 2014. 4. Sharma S, et al. The Journal of Physical Chemistry 2010.
5. Shih C-J, Vijayaraghavan A, Krishnan R, Sharma R, Strano, MS, et al. Nat Nano. 2011. 6. C. Bosch-Navarro et al. Nanoscale 2012.
Bilayer Graphene5
Oxidize and
ExfoliateReduce
Graphite GO rGO
COOH, OH, O-Adapted from6
Unique to our MIT lab
Carbon Nanotube Production Methods
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NPs Method Size Shape
Multi-wall Nanotube
chemical vapor deposition
(CVD) (1)
30 nm- 100 nm Rod
Vendor bulk Preparation (Sigma
755117)
Single-wall Nanotube
chemical vapor deposition
(CVD) (2)
<100 nm Rod
Vendor bulk Preparation:
(Sigma 755710)
HydrophilicHydrophobic
Corona
Hetero-
Polymer
Or Surfactant
Nanotube
Sonication
Suspended Nanotube
Surface properties are
critical to biodistribution
and clearance.2,3
1. Kudo A et al. Journal of the American Chemical Society. 2014.
2. Iverson NM et al. Nature nanotechnology. 2013.
3. Singh R et al. Proc. Natl. Acad. Sci. 2006.
Scalable SWNT Separation – MIT Technology
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Tvrdy K et al. ACS Nano. 2013.
Scalable
How does the chirality
influence nanotox?
Acknowledgements
NANOCELLULOSE SYNTHESIS
Douglas Bousfield, University of Maine
Cellulose Nanomaterials –
Potential applications and characterization challenges.
Doug Bousfield, Calder ProfessorDepartment of Chemical and Biological Eng.University of MaineOrono, ME 04469
Cellulose nanomaterials• Sustainable, renewable, recyclable, bio-compatable and
compostable.
Rheology Modifier
• Paints• Cosmetics• Food• Adhesives
Specialty Packaging
Herrera et al.
Vartiainen et al.
Tissue Engineering
• Scaffolds• Bandages• Ligament• Blood Vessels• Drug Delivery
Deng et al.
Fibers and Films
Dong et al., 2012
• Reinforcement• Textiles• Woven• Films
Foams
Paakko et al., Soft Matter, 2008
• Acoustic• Structural• Thermal• Absorption• products
Moon, R. J., Martini, A., Nairn, J., Simonsen, J., & Youngblood, J. (2011). Cellulose nanomaterials review: structure, properties and nanocomposites. Chemical Society Reviews, 40(7), 3941-3994.
Example application• Replace the aluminum coated polypropylene chip bag with
paper coated with cellulose nanofibers (CNF).
CNF provide the oxygen barrier that polymers are not able to obtain.
Product here could be recycled in the paper stream and would decompose if littered on the land or ocean
Potential contact with food.
Large volumes.
Key forms of cellulose nanomaterials
• Mechanically produced. Cellulose nanofibers (CNF), microfibrillatedcellulose (MFC)
• Chemically produced. Cellulose nanocrystals. (CNC)
• Bacterial cellulose. (BC)
Development of a lab based “loop grinder system” for CNF synthesis
• Mechanical methods. Ultra-fine friction grinder and pilot scale refiners.
Operate until “fines” content in fiber diameter sizer is over 90%
Challenges
• CNF is not easy to characterize. Fibers often are connected and can have web or ribbon type structures.
• Length of fibers even more difficult. Often the lengths are longer than the image.
• Chemical purity - cellulose is a natural material that is separated from biomass through chemical processes. Other trace chemicals are likely present as well as micro-organisms.
• Cellulose may be hard to detect in a biological system. There is no easy chemical signal compared to the background signals.
Initial steps-UPDATE• A lab based reactor was developed which allows a systematic
synthesis of CNFs
• First CNF materials were synthesized and expected to be shipped in December
• Working with Harvard to develop characterization methods for CNFs which is not trivial.
• CNF samples have been tested with AFM, SEM and TEM.
• What properties of importance for nanotox studies ?Fiber diameter? length? Node to node length?
Preliminary Characterization Data
• AFM images of tapping mode show that one
nanofiber has a width of 15-50 nm.
• The actual diameter is 52 nm
• Length several microns
Characterization Core
(David Bell, Georgios Pyrgiotakis)
Multi- Tier approach
Tier 1 characterization
• ENM core property characterization
– Size, shape, crystal structure/phase etc.
– Concentration for suspension particles.
• QA/QC procedures in place: TIER 1 characterization performed at
the Synthesis site and repeated at Harvard for QA/QC purposes
Tier 2 characterization
• ENM characterization expands to include
– Chemical composition, further surface functionalization, purity, etc
– Colloidal characterization in biological media of interest
– In-vitro dosimetric characterization
• Tier 2 may also include state of the art ENM specific characterization
– Chirality for CNTs, number of layers of Graphene/GO etc
– Endotoxin and bacteria characterization
Tier 1 Characterization: State of the art Analytical Methods
Properties Methods
Density Pycnometer
Specific Surface area BET
Porosity BET
Crystal Structure XRD, TEM-SAD
Primary Particle Size XRD-Rietveld analysis*, BET, TEM
Shape, Aspect ratio TEM-Image analysis
Size distribution TEM-Image analysis
Properties Methods
Hydrodynamic Diam. DLS
Crystal Structure TEM-SAD
Size TEM
Shape, Aspect Ratio TEM-Image analysis
Size distribution TEM-Image analysis, DLSSu
spe
nsi
on
sD
ry P
ow
de
r
*Crystallite size
Tier 2: Chemical Characterization
Properties Methods
Composition (Metal / Metal Oxide)ICP-MS, TEM-EDS, TGA, EC-OC,
Raman spectroscopy, FTIR
Composition (Carbon based
materials)EC-OC, Raman spectroscopy FTIR
Surface chemistry (for all ENMs) FTIR, XPS
Stoichiometry (Metals/Metal Oxides)ICP-MS (metals and oxides),
weight analysis (oxides)
Sterility and EndotoxinsBacteria Culture, Colorimetric
Assay
• Chemical composition, purity, endotoxin/bacteria
levels. etc
* For selected ENMs
Tier 2: Colloidal Preparation and Characterization in Biological
Media
• We are developing protocols for suspension preparation and
characterization
• ENMs will be dispersed in water and selected cell culture
media of interest.
• Colloidal Characterization will include:
Properties MethodsCritical Sonication Energy DLS
Size distribution DLS and TRPS,
Polydispersity DLS, TRPS
Zeta potential DLS, TRPS
Specific conductance DLS
pH pH meter
Effective density VCM, AUC
Dissolution* Dynamic Dialysis, ICP-MS
Corona Characterization* LC-MS
* For selected ENMs
Tier 2: Suspension prep, characterization in biological media
DeLoid et al., Nature Protocols , accepted , 2016
• We developed a detailed protocol that we plan to use for colloidal preparation, characterization and dosimetric analysis for low aspect ratio ENMs (Paper just accepted for publication in Nature protocols) COMPLETED
• All developed tools/protocols will be made available upon request . Training can also be provided if needed.
• We plan to start working developing will develop new methods for high aspect ratio materials such as CNTs and 2D ENMs etc (Method development core)
Characterization Reports
Reference Material
Repository Core
Dr. Georgios Pyrgiotakis, Center Coordinator
Priorities for year 1:
1. Establish an ENM Centralized Repository (Harvard) (Completed)
– Develop storage guidelines Completed
– Develop shipping guidelines Completed
2. Development of a web-based database to include all data for synthesis, characterization and nanotox studies (in progress, End of of 2016)
3. Development of web based portal for communication purposes with nanotox consortium (in progress, End of of 2016)
ENM and data flow diagram
• Development of the ENM repository lab
– Center Coordinator will be in charge on the day-to-day operations
• Electronic database – Synthesis information (SOPs for each ENM, etc)
– Characterization data (Tier 1 and Tier 2)
– NHIR labs will be able to request ENMs electronically
– All related publications for reference ENMs will be archived and made available
online
Electronic
Database
Synthesis
ENMs
NHIR Nanotox
Researchers
ENM Central
Repository at
Harvard
Data
ENMs
Data
NIEHS Database
ENM Storage, handling and shipping: UPDATE
– ENMs after synthesis to be stored in controlled
environmental conditions (Ar atmosphere, UV protection,
low RH/O2 levels, etc)
– Develop guidelines for containers to be used to store
ENMs inclusive of cleaning procedures, type of containers
etc) (COMPLETED)
– Develop shipping guidelines (COMPLETED)
Central ENM Repository Lab (Harvard)
• MBRAUN glovebox
– Maintains <0.1ppm H2O, <0.1ppm O2 levels at all times.
– Argon atmosphere, UV shield, RH, T logging
Working area
• ENM
packaging
• ENM sample
preparation
etc.
Storage area
Airlocks
Container prep area
Particle free
hood for
container
preparation
ENMs packing and
preparation area
Methods Development Core
Philip Demokritou
Development of methods to
concentrate ENM suspension for
nanotoxicology research
Challenge
• All ENMs in suspensions were stored at 50ug/mL to ensure size stability over time
• Higher concentrations of ENMs in suspension might be needed for nanotox research.
• Challenge: How to concentrate the ENM suspension without altering important colloidal characteristics such as Hydrodynamic Radius.
• Currently we are exploring two methods:
– Centrifugation (not recomended):• Spin the suspension at high RPMs (5000 and above) and remove
supernatant.• Pros: This method concentrates the ENMs but does not alter the ionic
strength of the solution.• Cons: 1) The ENMs can aggregate 2) It varies with particle size and
material 3) Limited quantity (300 ml)
– Vacuum Evaporation/Rotary Evaporator:• Evaporate the water under vacuum at 30 C. • Pros: 1) Very precise control of the evaporation and minimum chance
of forming aggregates 2) Can concentrate up to 1 l at a time.• Cons: Concentrates salts and ions that can complicate interactions in
biological media.
Vacuum Evaporation/Rotary Evaporator
• The rotary evaporator can effectively concentrate the suspension by a factor of 10 without significantly impacting the particle size distribution (diameter and PDI).
• WE are working on:
– Evaluating long term stability of the suspension
– Develop a method for estimating the concentration beyond the concentration factor.
10 x
Assesing food-iENM and GIT-iENM interactions:
iENM transformations and effects on bio-kinetics and toxicity
Project: Ingested ENMs (iENMs)
Food and GIT ENM Transformations:
Development of a lab based GIT simulator for assessment of iENM transformations
Stomach
• pH 1-3
• Enzymes
• Salts
• Biopolymers
• Agitation
• 30 min – 4
hours
Figure 1. Food-borne inorganic nanoparticles (NPs) experience different physicochemical conditions in the digestive tract that influence the biological fate and potential toxicity of these NPs.
Foodborne Inorganic Nanoparticles (NPs)
Small Intestine
• pH 6-7.5
• Enzymes
• Salts, Bile
• Biopolymers
• Agitation
• 1 – 2 hours
Mouth
• pH 5-7
• Enzymes
• Salts
• Biopolymers
• 5 – 60 s
• Challenges: Characterization of iENM transformations in complex media – New ENM characterization methods need to be developed
Development of Standardized methodologies
across the suspension preparation-
characterization- dosimetry continuum for 2D
and high aspect ratio ENMs
In Collaboration with Prof. Strano at MIT
Development of Methods for in-vitro dosimetry for high aspect ratio and 2D materials for in-vitro studies
DeLoid et al., Nature Protocols , accepted, 2016
• We have developed standardized methodologies for low aspect ratio
ENMs across the suspension preparation-characterization-dosimetry.
• Expand to include 2D and high aspect ratio ENMs
Advanced Characterization Algorithms for Polydispersity
Characterization
High-Throughput Single
Particle Tracking
(movie)
Single Particles
Bundles
Temporal Comparisons
Aggregation Surface Binding Degradation
Shifts in Size Distribution
Properly handling polydispersity and complexity in nanoparticle dispersions remains
a challenge
We are developing a next generation of characterization tools to address this.
Corona Characterization on Carbon
Nanotubes
In Collaboration with Prof. Strano at MIT
New Methods to Understand the Soft Corona
62
Wrapping
molecule
Plate Reader nIR
q/Kd [M-1] q Kd [uM]Kd
[uM]
(GTTT)7
319.8
[231 408.6]
9.24*10-3
[-41.3 59.8] *10-3 28.910.55
[5.22 15.89]
SC 335.7
[268 403.5]∙ ∙ ∙
SDS391.7
[273.1 510.4]∙ ∙
0.85
[0.60 1.10]
(GT)15
444.2
[359.5 528.9]
9.36*10-3
[-18.5 37.17] *10-3 20.815.83
[4.30 7.37]
(AT)15
488.9
[201.1 776.7]
3.76*10-3
[-8.78, 16.3] *10-3 7.527.34
[5.92 8.76]
SDBS498.4
[381.9 614.8]∙ ∙ ∙
SDS+SC 770.2
[665.7 874.8]∙ ∙
1.07
[0.77 1.36]
Dextran1174
[1105 1244]∙ ∙
1.067
[0.89 1.24]
PS(MW 200k)
1182.9
[936.5 1429]
3.73
[-2.81, 2.82]339.06
3.15
[2.66 3.63]
Chitosa
n2097
[1633 2562]
5.88*10-3
[1.06 10.71] *10-3 2.8112.17
[9.39 14.95]
PS (MW 70k)
2439.5
[1801 3078]
1.37*10-2
[-2.01 4.76] *10-2 5.60 ∙
Inve
rse
rib
ofla
vin
(p
rob
e)
ad
so
rptio
n (
1/m
M)
Inverse riboflavin (probe) concentration (1/uM)
Using a method under development, we use standardized probe molecules such as
riboflavin to probe the soft corona phase around suspended nanoparticles.
The method can quantify the number of binding sites (q) within and on the soft
corona as well as the dissociation constant (Kd)
Kd can then be compared to other methods
Trend yields q and Kd
for each probe and
each corona phase
Assessment of ENM stability over time under environmental conditions: Effects on biological
activity
Investigating and Documenting ENM Stability
MAIN CONCERN – PCM changes due to storage/handling conditions lead to measurable biological outcomes
• Surface OXIDATION (aging, passivation)
• DISSOLUTION & subsequent chemical transformations
• SURFACE exchange phenomena (adsorption of organics, exchange of cations & anions)
• ?
• THESE ARE LARGELY SURFACE - DRIVEN PHENOMENA !!!
and SURFACE CHEMISTRY RULES!
Methods – Stability
• Representatives of ENM classes
– Metals
– Metal Oxides
– 2-D materials - Graphenes
– Nano cellulose
– ?
• Identify and monitor signature properties over time under
relevant storing and handling/processing condition
– Define relevant scenarios – dry vs. wet
– Develop initial SOP based on existing best practices
– Investigate stability for each scenario
– Incorporate findings into revised SOPs
Signature Markers
• Surface oxide thickness
– XPS, High Res TEM
• ROS generation, Surface activity index
– FRAS & direct oxidation of other probes (Trolox)
• Organics on the surface
– TGA, TGA/GC-MS, …
• Other properties - material specific
– Can we take advantage of new sensor technologies ?
Administration and Research
Coordination Core
Philip Demokritou
Administration and Research Coordination Core (ARCC)
68
A hierarchical organizational structure inclusive of an External Science
Advisory Committee
Center Director- PIP. Demokritou
Center CoordinatorG. Pyrgiotakis
ESAC
(5 people,)Steering Committee
(D. Bell, D. Bousfield, B. Moudgil, M. Strano)
External Scientific Advisory Committee( ESAC)
• Dr Vince Castranova (Former NIOSH- HELD Nano-program
Director, currently at UWV)
• Professor Sotiris Pratsinis ( ETH, Zurich, ENM synthesis)
• Professor Ahmed Bushnaina (NEU, Director, NSF Nano-
manufacturing Center)
• Professor Robert Hurt ( Brown U., ENM synthesis and Nanotox)
• Dr Treye Thomas ( US CPSC, Nano-program Director )
Research Integration Activities for Year 1
Research Integration:
• Discussion/visits with NHIR investigators and NIEHS program officer to
identify areas for collaborative research on method development
and support on current research activities ( fall 2016)
• Annual meeting and symposium for Harvard-NIEHS Center to present
our work and promote integration/collaboration among its members.
NHIR investigators are welcome to attend!
• NIEHS annual meeting (December 2016 @ NIEHS, Harvard for 2017?? )
Communications./Outreach:
• Develop a Center Website to outline core activities of the Center (in
progress, to be completed in December ).
• Nanolecture series: (webcast) to start in January 2017. Seminars from
leaders in application/material. NHIR members are welcome to
present their research
• Publications, conference presentations ( 2 papers are in submission)
Reference ENMs: Timeline
Year 1
Timeline for year 1
2016
October 15, 2016
• Al2O3 (~20 nm) (FSP)
• SiO2 (~15 nm) (FSP)
• Au* (15 nm) (WS)
December 31, 2016
• SiO2/Ag 5% w/w Ag (FSP)
• SiO2/Ag 20% w/w Ag (FSP)
• Cellulose Nanofibrils (CNFs)
• CeO2 (two sizes)(FSP)
• Fe2O3 (two sizes) (FSP)
March 31, 2017
• Graphene
• Graphene Oxide
• Cellulose Nanocrystals
2017
Other ENMs that can be made available in year 1, if needed:
• Comparative Materials: Welding fumes? GRAS materials for iENM studies
(TiO2, SiO2)
• Other Me/MeO: MnS, ZnS ?
FSP: Flame Spray Pyrolisis(Powder form).
WS: Wet synthesis (suspension). ENMs will be citrate capped. Other capping agents can be made available
Thank You!