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 andproteins as a result of various genome sequencing projects demands increasedscales of analysis. We have recently developed two closely relatedapproaches to molecular analysis and separation that employ flow basedanalytical instrumentation, magnetic nanoparticle technology, and SQUIDsensors. Target molecules are conjugated to magnetic microspheres such thatthe magnetic moment of the microsphere uniquely identifies the targetmolecule bound to that microsphere. The "magnetic flow spectrometer"system separates the magnetic microspheres based on their magneticmoments, enabling highly parallel continuous flow biomolecular separationson a preparative scale, and revolutionising our ability to identify potentialdiagnostic or therapeutic targets. The "magnetic flow cytometer" combines anovel SQUID-based magnetic target molecule identification concept withfluorescence-based analyte detection enabling multiplexed target-analyteanalysis in flow. Time-correlated magnetic and fluorescence measurements ina flow cell identify the target molecule (magnetic moment) and the targetanalytebinding (using fluorescent tags).