A new sensing system is described that is based upon the aggregation of nanoparticles by a target biological analyte and the dielectrophoretic impedance measurements (DEPIM) of the aggregates. A key aspect was bridging the interface between inorganic nanoparticles and water-soluble, biologically active moieties. Di-functional, asymmetric poly(ethylene glycol) (PEG) linkers of various molecular weight and chain end functionality were prepared by either end group interchange or anionic ring opening polymerization. Molecular weights ranged from 350 g/mol to 7,200 g/mol with chain end functionalities including azido, allyloxy, amino, siloxy, carboxy, cyano, hydroxy, tetrahydropyran, and mercapto. These linkers were employed to disperse CdS SiO2, SiO2, poly(styrene) (p(St)), Au/p(St) and Au/SiO2 nanoparticles of various sizes (20 nn to 5 mum) in water. Preliminary systems focused upon the aggregation of biotinylated nanoparticles in the presence of avidin. We thoroughly explored how particle functionality, grafting density, particle size, PEG linker length, and particle composition will affect the aggregation mechanism. Proteins, anti-bodies, and small molecule analytes were able to induce aggregation demonstrating the versatility of this sensing mechanism. Finally, a series of microfluidic devices were prepared to demonstrate real-time sensing ability. Initial DEPIM were able to selectively detect target analytes at the nanomolar level, and show promise of reaching the picomolar level upon optimization.