SGER: Development of NMR relaxation theory for colloidal aggregates of superparamagnetic nanoparticles

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

NON-TECHNICAL DESCRIPTION: Superparamagnetic iron oxide nanoparticles (SPIO) are being developed as MRI contrast agents to detect diseases such as cancer and atherosclerosis. These systems of aggregating colloidal ceramic nanoparticles are of particular interest to the medical community for in vivo sensing and imaging, and in vitro diagnostics. The sensors operate by clumping together in the presence of the chemical of interest. A lack of a consistent theory describing the operation of these sensors hinders the advancement of these applications. This project aims to develop such a theory and to create a framework for engineering the SPIO sensors for optimal and reliable performance. The theoretical work will be supported experiments to explore nanoparticle properties. Conventional techniques do not have the capabilities to perform the necessary number of measurements to make the development of the theory practicable. A custom-built one of a kind instrument that is capable of thousands of measurements a day will be used to provide data for and experimentally verify the theory. This project will involve training of one graduate student. TECHNICAL DETAILS: The proposed research will enable aggregation based assays or imaging modalities by providing the scientific basis to engineer superparamagnetic nanoparticles. Challenges include achieving specificity, higher signal to noise, and particle optimization (core composition and size, ligand density, etc.). There are as yet no design rules to guide the chemist on the best aggregation state to achieve high sensitivity and stability. This research will enable innovation in medical diagnostics and in vivo imaging. Current attempts at modeling aggregation use empirical theories developed for unaggregated particles. The fractal aggregates are represented as a single large particle on which the outer sphere diffusion theory is applied. This approach ignores the water molecules' ability to access the inner parts of the aggregate and only applies over a narrow range of conditions. Computer simulations are being developed that account for the diffusion of water within the fractal aggregate and address the discrepancy observed at higher Larmor frequencies. SPIO nanoparticles of different size and aggregate configuration are being developed to provide data for the theoretical model. Conventional NMR relaxometers do not lend themselves to high-throughput measurements required for a comprehensive study. A custom-built high-throughput NMR relaxometer is being used to aid the formulation of a new theory. The instrument enables hundred of parameters to be investigated quickly and efficiently.