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Nanoparticle Measurements and Standards for Biomedical Applications and Health

Summary:

Our goal is to develop certified reference materials, standard test methods, measurements, and critical data for the physicochemical characterization of engineered and multifunctional nanoparticles. This body of information will enable widespread acceptance and adoption of nanotechnologies for the diagnosis, treatment, and prevention of human disease, as well as enable evaluation of the environmental, health, and safety (EHS) risks of nanomaterials.

Description:

Atomic force microscopy image of gold nanoparticles on substrate

Taking nanoparticle therapeutic and diagnostic platforms from the laboratory to the clinic requires a well-defined pre-clinical route for FDA approval that must include widely adopted and standardized procedures for assessing the efficacy and toxicity/health risk of new nanomaterials. Certified reference materials underpin the approval procedures and enable interlaboratory comparison and benchmarking. To this end, we are working to develop measurement protocols (assays), consensus standard test methods, and computational tools for the physicochemical characterization of different nanoparticle classes under physiologically and environmentally relevant conditions. Particle properties characterized include size and size distribution, surface area, surface charge, zeta potential, crystallinity, aggregation, stability, transport characteristics, chemical composition, purity, and photothermal/plasmonic behavior.

Impact and Customers:

  • NIST Gold Nanoparticle Reference MaterialsAnnual healthcare costs associated with cancer treatment exceed $188 billion, yet the mortality rate for cancer in 2002 was identical to that in 1950. According to the National Cancer Institute (NCI), "nanotechnology will change the very foundations of cancer diagnosis, treatment, and prevention."
  • NIST collaboration with NCI and the Food and Drug Administration (FDA) provides a framework for developing a standardized analytical cascade for physical and biological characterization of nanoparticles for imaging, diagnosis and therapy.
  • New consensus standards for characterization of biomedical nanoparticles are currently under development within ASTM committee E56 on Nanotechnology.
  • NIST interactions with NCI, FDA, the National Institute of Occupational Safety and Health (NIOSH), and the National Toxicology Program (NTP) have fostered robust interagency cooperation and enabled us to focus our resources on nanoparticle standards priorities for the biomedical and EHS sectors.

Major Accomplishments:

Engineered nanoparticles hold great promise for the detection and treatment of disease. Advanced applications in cancer management, for instance, could result in precise in situ imaging and localization of tumors and targeted application of therapeutic agents directly to tumor cells. To bring these technologies to the clinical stage, and enable assessment of the EHS aspects of nanoparticles, we are partnering with FDA and NCI, and working with NIOSH, NTP and others, to develop a nanoparticle measurement infrastructure.

Standards
Last year NIST issued its first reference standards for nanoparticles targeted at the biomedical research community —literally, “gold standards” for labs studying the biological effects of nanoparticles. This effort involved an extraordinary level of cooperation among seven NIST divisions. The three new reference materials (RMs), different size citrate-stabilized gold nanoparticles, were developed to address a need identified by the cancer research community. Current efforts are focused on the development of nanoscale titanium dioxide and silver RMs for assessing the potential health risks and biological interactions associated with nanomaterials.

Working with ASTM and other international standards development organizations, we are making progress in standardizing measurements and protocols that are urgently needed by the nanotechnology community. This past year NIST and NCI jointly organized three interlaboratory studies to evaluate physical and biological tests on nanomaterials. A report on these studies will be published by ASTM and data will be used to develop precision statements for ASTM standards. Also this past year we hosted and jointly coorganized (with NCI) a workshop on enabling standards for nanomaterial characterization to address the lack of standardized and validated protocols. One major outcome of this meeting is the development of a community driven wiki site to facilitate pre-standard development of protocols and reference materials. 


Measurements
Developing a viable measurement approach for quantifying the dispersion quality of nanoparticles such as carbon nanotubes within a liquid medium or solid matrix remains a challenge due to the variety and complexity of aggregative morphologies that can result. Working with industry and academic partners, we have applied quantitative ultra small-angle X-ray scattering (USAXS) methods to a range of single- and multi-wall carbon nanotube (SWCNT and MWCNT) dispersions and composites. A three-component morphology model has been applied to interrogate CNT structures in dispersions. The relative prominence of these components, together with their respective characteristic sizes or persistence lengths, can be related to the observed scattering. When combined with constraints such as the known C mass loading, the model can be used to infer the degree of filling of the tube interiors. The information obtained has implications for the application of CNTs in biomedical and other applications.

USAXS data from SWCNT dispersion

USAXS data from a SWCNT dispersion with 3-component model fit decomposition


We have also developed different flow-cell configurations to augment the USAXS and SAXS instrumentation located at the Advanced Photon Source (APS, Argonne, Illinois), a 3rd generation synchrotron source. Working with collaborators at the University of Maryland, Columbia University and APS, we have utilized these flow-cells to study the nucleation, growth, dispersion, and structure of technologically important nanoscale materials. Examples include quantitative correlation of the diameter and aspect ratio of solution-suspended gold nanowires with their agglomeration and flow characteristics, and interrogation of the homogeneous solution-phase precipitation of nanocrystalline cerium oxide particles in the 2 nm to 12 nm size range.
Dendron conjugated gold nanoparticle

Start Date:

October 27, 2008

End Date:

ongoing

Lead Organizational Unit:

mml

Staff:

Contact
Vincent A. Hackley
(Ceramics Division)
(301) 975-5790
vince.hackley@nist.gov