A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.
A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts the electric field created by an AC voltage and forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping via cell-sized posts coupled with a drag-DEP force balance, we show that separation of similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence.
['Douglas|Temple Anne|TA|', 'Cemazar|Jaka|J|', 'Balani|Nikita|N|', 'Sweeney|Daniel C|DC|', 'Schmelz|Eva M|EM|', 'Davalos|Rafael V|RV|']
D000818:Animals D045744:Cell Line, Tumor D002469:Cell Separation D003198:Computer Simulation D046209:Electrophoresis, Microchip D004867:Equipment Design D005240:Feasibility Studies D005260:Female D006801:Humans D056656:Lab-On-A-Chip Devices D055595:Mechanical Phenomena D051379:Mice D008810:Mice, Inbred C57BL D008839:Microelectrodes D008962:Models, Theoretical D009038:Motion D009369:Neoplasms D010051:Ovarian Neoplasms
Biophysics Tumor Microfluidics Cell separation Heterogeneity