Atomic Force Microscope (AFM) Nanoparticle Metrology

The largest existing market for nanotechnology centers on production and use of nanoparticles and nanocomposites. The NextGen Program is developing techniques for fixing soft, bio-mimetic nanoparticles on surfaces without distorting or denaturing them, so that they can be examined with atomic force microscopy (AFM). Medical applications range from imaging contrast agents to therapeutic cancer treatments. Advances in optical tweezers (OT) technology will allow manipulation of particles with sizes reaching down to the nanoscale, giving OT promise as a nanopositioning and nanoassembly tool. Carbon nanotubes, fuel cell membranes, and cellulose nanocrystals (CNCs) are among the challenging materials for which advanced SEM, OM, and AFM techniques are being investigated.

Recent policy statements by the US Food & Drug Administration (FDA) and the National Cancer Institute (NCI) indicate that there is a need to improve the efficiency and effectiveness of new drug and medical device development from the research laboratory to the clinic. According to these documents, this can be achieved by formally incorporating physical and chemical characterization assays alongside traditional biochemical and biology-based ones [1, 2]. The expectation is that quantitative physical measurements and standards arising from an alliance of the FDA, NCI, and NIST will accelerate the translation of nanotechnology-based approaches from the laboratory, increasing the likelihood that these approaches will ultimately be of direct application for human benefit. This project focuses on applying advanced AFM-based techniques to optimize the formulation and manufacturability of targeted nanoparticle delivery systems (NDS). NDS are a platform for encapsulating diagnostic imaging agents and therapeutics for treatment of cancer and other diseases. The anticipated benefits of this approach being greatly reduced costs and side effects. For example, we reported on the characterization of a magnetic resonance imaging (MRI) contrast agent within a targeted NDS complex developed by one of our collaborators earlier this year [3].

[1] National Cancer Institute, “Cancer Nanotechnology Plan: a strategic initiative to transform clinical oncology and basic research through the directed application of nanotechnology,” July 2004.

[2] Food & Drug Administration, “Challenge and opportunity on the critical path to new medical products,” March 2004.

[3] J. A. Dagata, N. Farkas, C. L. Dennis, R. D. Shull, V. A. Hackley, C. Yang, K. F. Pirollo, and E. H. Chang, “Physical characterization methods for iron-oxide contrast agents encapsulated within a targeted liposome-based delivery system,” Nanotechnology 19 305101(2008).

• Demonstrated optimized methods for immobilizing intact liposome-based nanoparticle delivery systems (NDS) for scanning probe microscope (SPM) imaging and characterization under fluid conditions, a critical first step for quantitative measurements. 
• Evaluated improved magnetic coatings for fluid and dry magnetic force microscopy (MFM) for characterizing dispersed and aggregated magnetic resonance imaging (MRI) contrast enhancement agents.  Improving the contrast agents increases sensitivity for imaging smaller features, like incipient tumors.