A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow
| Autor: | Daniel C. Sweeney, Temple A. Douglas, Rafael V. Davalos, Eva M. Schmelz, Nikita Balani, Jaka Cemazar |
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| Rok vydání: | 2017 |
| Předmět: |
Clinical Biochemistry
Microfluidics Nanotechnology Cell Separation 02 engineering and technology 01 natural sciences Biochemistry Article Analytical Chemistry Electrophoresis Microchip Mice Motion Cell Line Tumor Lab-On-A-Chip Devices Neoplasms Fluid dynamics Animals Humans Computer Simulation Treatment resistance Mechanical Phenomena Ovarian Neoplasms Chemistry 010401 analytical chemistry Aggressive cancer Equipment Design Models Theoretical Force balance Dielectrophoresis 021001 nanoscience & nanotechnology 0104 chemical sciences Mice Inbred C57BL Drag Biophysics Feasibility Studies Female Fluid motion 0210 nano-technology Microelectrodes |
| Zdroj: | ELECTROPHORESIS. 38:1507-1514 |
| ISSN: | 1522-2683 0173-0835 |
| DOI: | 10.1002/elps.201600530 |
| Popis: | 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 channel of the electric field created by an AC voltage across a microfluidic channel and which 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 on cell-sized posts by a drag-DEP force balance, we show that separation of very 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. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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