Nanoparticle Metrology and Standards for Biomedical Applications and Health

Our goal is to develop certified reference materials, standard test methods, measurement protocols, 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.

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:

• Annual 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.

Nanoparticle-based vectors 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, sensitive ex situ diagnosis, and targeted application of therapeutic agents directly to tumor cells. To bring these technologies to the clinical stage, and enable assessment of the environmental, health and safety aspects of nanoparticles, we are partnering with FDA and NCI, and cooperating with NIOSH, NTP and others, to develop a nanoparticle measurement infrastructure.

This year NIST issued its first reference standards for nanoparticles targeted for 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),citrate-stabilized gold particles nominally 10 nm, 30 nm and 60 nm in diameter, were developed to address critical needs identified by the cancer research community. Particle dimensions were quantified using six independent methods.

Simulated temperature profiel of defective nanoshells

Characterization information provided for the RMs include gold content, major ion concentrations, pH, conductivity, zeta potential and endotoxin analysis.

An important focus of this project is the development of new measurement approaches and computational tools to facilitate the study of nanoscale materials under biologically relevant conditions. An example involves the optical activation of gold-nanoshells with laser radiation in the near-IR spectrum, which is used as a means of inducing hyperthermia in a tumor while leaving the surrounding healthy tissue intact. We have initiated model-based studies in which the goal is to elucidate the influence of particle agglomeration and shell defects on the local heat transfer behavior of the particles.

Gold Nanoshell

In another example, the high aspect ratio, controlled dimensions, and narrow size distributions of nanowires obtainable by template-electrodeposition is of interest for biomedical applications such as drug delivery and biosensors. In situ studies of particle dispersion, alignment and flow could provide a key to understanding the behavior of these nanowires in the circulatory system. To this end we have recently developed various flow cells for the ultrasmall-angle X-ray scattering (USAXS) instrument at Sector 32 of the Advanced Photon Source (APS, Argonne, Illinois). Working with collaborators at the University of Maryland and APS, we have quantitatively correlated the diameter and aspect ratio of solution-suspended gold nanowires with their agglomeration and flow characteristics. This research has provided the first quantitative measurement of gold nanowire alignment under convergent flow conditions, and a summary has been submitted for publication in the journal Nanoletters.

Extensional flow of gold nanowires