The quest for new cell-free DNA and exosome biomarker-based molecular diagnostics require fast and efficient sample preparation techniques. Conventional methods for isolating these biomarkers from blood are both time-consuming and laborious. New electrokinetic microarray devices using dielectrophoresis (DEP) to isolate cell-free DNA and exosome biomarkers have now greatly improved the sample preparation process. Nevertheless, these devices still have some limitations when used with high conductance biological fluids, e.g. blood, plasma, and serum. This study demonstrates that electrochemical damage may occur on the platinum electrodes of DEP microarray devices. It further examines two model device designs that include a parallel wire arrangement and a planar array. Effective isolation of fluorescent beads with parallel wires is shown under low-conductance conditions (10(-4)S/m), but electrothermal flow overcomes DEP forces under high conductance conditions (>0.1S/m). Planar devices are shown to be effective under high conductance conditions (approximate to 1S/m) without the deleterious effects of electrothermal flow. This study provides new insights into design compromises and limitations for producing future electrokinetic devices for better performance with high conductance solutions.