Bioassay with magnetic particles in flow: a method forhighly parallel molecular separations of complexbiological systems

摘要

The huge increase in the amount of information about genes andrnproteins as a result of various genome sequencing projects demands increasedrnscales of analysis. We have recently developed two closely relatedrnapproaches to molecular analysis and separation that employ flow basedrnanalytical instrumentation, magnetic nanoparticle technology, and SQUIDrnsensors. Target molecules are conjugated to magnetic microspheres such thatrnthe magnetic moment of the microsphere uniquely identifies the targetrnmolecule bound to that microsphere. The "magnetic flow spectrometer"rnsystem separates the magnetic microspheres based on their magneticrnmoments, enabling highly parallel continuous flow biomolecular separationsrnon a preparative scale, and revolutionising our ability to identify potentialrndiagnostic or therapeutic targets. The "magnetic flow cytometer" combines arnnovel SQUID-based magnetic target molecule identification concept withrnfluorescence-based analyte detection enabling multiplexed target-analyternanalysis in flow. Time-correlated magnetic and fluorescence measurements inrna flow cell identify the target molecule (magnetic moment) and the targetanalyternbinding (using fluorescent tags).