OTHER FUNCTIONS - NOVEL TECHNOLOGIES FOR ASSESSING LIPOPROTEIN SUB-FRACTIONS

Global analysis of serum lipoprotein subclasses requires a platform that measures size distributions of lipoprotein particles identified by apoprotein content. We propose to employ an innovative methodology based on superparamagnetic and birefringent nanoparticles that bind to supramacromolecular assemblies through a ligand for a specific component of the assembly. The application of a pulsed, homogeneous magnetic field across the sample causes the magnetic nanoparticle complexes to align magnetic moments in the direction of the field. After the field is quenched, the complexes relax to random orientations with rate constants that scale with the hydrodynamic volumes of the complexes. The orientation and relaxation of the magnetic nanoparticle complexes is monitored optically using intrinsic birefringence provided by the nanoparticles and field modulated light scattering provided by the entire complex. By using sufficiently small and homogeneous nanoparticles the optical measurements can be made in the presence of unbound nanoparticles. For Phase I proof of concept we will use nanoparticles conjugated to antibodies against apolipoprotein B100/48, which binds to B100 on VLDL, IDL and LDL, and to B48 on chylomicrons. The birefringence and light scatter relaxationkinetics will provide both concentrations and size distributions of these lipids in serum without sample pre-processing.