Electrokinetic device design and constraints for use in high conductance solutions

Abstract

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 S/m), but electrothermal flow overcomes DEP forces under high conductance conditions (>0.1 S/m). Planar devices are shown to be effective under high conductance conditions (∼1 S/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.

Electrically driven microfluidic platforms for exosome manipulation and characterization

“…[38] and Heineck et al. [54]) described alternatives to reduce this undesired effect. In the case of Ayala Mar et al., fresh solution was constantly injected into the insulator‐based microfluidic channel by EOF, reducing the solution residence time within the confines of the device and resulting in low heating.…”

Microfluidic device for on-chip isolation and detection of circulating exosomes in blood of breast cancer patients

“…Microfluidics provides an effective platform for manipulating small quantities of exosomal samples with enhanced purity capabilities and precision. 17,18 The techniques developed so far for microfluidics-based exosomal isolation are based on physical characteristics (size, [19][20][21][22][23] density, 24 and electrical properties [25][26][27] ) and/or biological characteristics (antibody-antigen reaction [28][29][30] and aptamers 31,32 ). Although physical microfluidic techniques have shown unique advantages for label-free and high-throughput isolation, these approaches have not completely distinguished exosomes as a specific population apart from other vesicles with similar sizes and densities.…”

Simple and Low‐Cost Sampling of Cell‐Free Nucleic Acids from Blood Plasma for Rapid and Sensitive Detection of Circulating Tumor DNA

“…Measurement of cfDNA Integrity and Cellular DNA Background : To measure the cfDNA integrity, cfDNA was amplified with two types of Alu primer sets using real‐time PCR . The cfDNA samples were analyzed using the Alu 247/115 ratio.…”

“…In addition, they require chaotropic reagents for blood cell lysis that can lead to the release of DNA from noncancerous cells, which can strongly affect ctDNA analysis. Although recent cfDNA isolation methods that do not use centrifuges have been developed, they still need additional instruments, such as vacuum systems and DC power supplies for fluorescence labeling . To overcome this issue, procedures of cfDNA sampling from blood plasma need to be standardized to obtain a sufficient amount of DNA and reduce the cellular background, which would subsequently improve the detection sensitivity of ctDNA mutation profiling.…”