Analytical Chemistry · 2000 · 416 citations · 32 references
PharmacyCell BiologyHematologyBioseparationsSeparation ProcessesSeparation ScienceCell IsolationCell SeparationField-flow FractionationMicrofluidic DevicesMicrofluidicsDielectrophoretic Cell SeparationDielectrophoretic SeparationHematopoietic Stem Cell IsolationLeukocyte Subset SeparationVelocity Profile Analysis
DEP‑FFF enables bulk separation of clinically relevant cell types—such as breast cancer cells from T‑lymphocytes, CD34+ stem cells, and leukocyte subpopulations—by exploiting intrinsic dielectric properties. In a thin chamber with a microfabricated interdigitated electrode array energized by AC signals, cells are levitated by the balance of dielectrophoretic and sedimentation forces to distinct equilibrium heights and then separated by differing velocities within a velocity profile, a process that can be electronically tuned. The method requires no labeling, yields viable cells for downstream culture or analysis, and can be scaled for routine laboratory use or miniaturized implementation.
Dielectrophoretic field-flow-fractionation (DEP-FFF) was applied to several clinically relevant cell separation problems, including the purging of human breast cancer cells from normal T-lymphocytes and from CD34+ hematopoietic stem cells, the separation of the major leukocyte subpopulations, and the enrichment of leukocytes from blood. Cell separations were achieved in a thin chamber equipped with a microfabricated, interdigitated electrode array on its bottom wall that was energized with AC electric signals. Cells were levitated by the balance between DEP and sedimentation forces to different equilibrium heights and were transported at differing velocities and thereby separated when a velocity profile was established in the chamber. This bulk-separation technique adds cell intrinsic dielectric properties to the catalog of physical characteristics that can be applied to cell discrimination. The separation process and performance can be controlled through electronic means. Cell labeling is unnecessary, and separated cells may be cultured and further analyzed. It can be scaled up for routine laboratory cell separation or implemented on a miniaturized scale.
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Microfluidic Diffusion-Based Separation and Detection
Bernhard H. Weigl, Paul Yager · Science · 1999 · 501 citations
Dielectrophoretic separation of cancer cells from blood
Peter R. C. Gascoyne, Xiaobo Wang, Ying Huang et al. · IEEE Transactions on Industry Applications · 1997 · 405 citations · Full text