Rare cell capture in microfluidic devices

This article reviews existing methods for the isolation, fractionation, orcaptureofrarecellsin microfluidic devices. Rare cell capture devices face the challenge of maintainingtheefficiencystandard of traditional bulk separation methods such as flow cytometersandimmunomagneticseparatorswhile requiring very high purity of the target cell population, whichistypicallyalreadyatverylowstarting concentrations. Two major classifications of rare cell capture approaches arecovered: (1) nonelectrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheathflowandstreamlinesorting) arediscussedforapplicationsusingbloodcells, cancer cells, and other mammalianc ells, and (2) electrokinetic(primarilydielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/orpurity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of currentstudiesonlyprocess spiked cell lines or pre-diluted/lysedsamples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as wellastheelectrokineticand non-electro kinetic methods that can potentially be combined to improve performance in future studies. (C) 2010 Elsevier Ltd. All rights reserved.