Emerging on‐chip electrokinetic based technologies for purification of circulating cancer biomarkers towards liquid biopsy: A review

Abstract

Early detection of cancer can significantly reduce mortality and save lives. However, the current cancer diagnosis is highly dependent on costly, complex, and invasive procedures. Thus, a great deal of effort has been devoted to exploring new technologies based on liquid biopsy. Since liquid biopsy relies on detection of circulating biomarkers from biofluids, it is critical to isolate highly purified cancer‐related biomarkers, including circulating tumor cells (CTCs), cell‐free nucleic acids (cell‐free DNA and cell‐free RNA), small extracellular vesicles (exosomes), and proteins. The current clinical purification techniques are facing a number of drawbacks including low purity, long processing time, high cost, and difficulties in standardization. Here, we review a promising solution, on‐chip electrokinetic‐based methods, that have the advantage of small sample volume requirement, minimal damage to the biomarkers, rapid, and label‐free criteria. We have also discussed the existing challenges of current on‐chip electrokinetic technologies and suggested potential solutions that may be worthy of future studies.

Machine Learning Approaches in Label-Free Small Extracellular Vesicles Analysis with Surface-Enhanced Raman Scattering (SERS) for Cancer Diagnostics

“…Microfluidic devices based on electrokinetics represent a category of tools designed to isolate sEVs using external electrical forces, eliminating the need for tagging or labeling specific molecules of interest. 17, 18 The dielectrophoresis (DEP) phenomenon, harnessed in these devices, enables precise isolation based on the dielectric properties and size distribution of sEVs under a non-uniform electric field, offering a rapid and label-free approach. This non-uniform electric field can be generated through the application of an alternating current across an array of electrodes 19, 20 or by employing an insulator-based dielectrophoretic (iDEP) strategy using obstacles such as micro-pillars in microfluidic channels.…”

Liquid Metal Electrodynamic Accumulation Microfluidics System for DNA Memory and Liquid Biopsy

“…[ 1–5 ] The use of electrokinetic systems enables the precise control of DNA molecules, which is crucial for systematic DNA memory processes, DNA origami manipulation, and cell‐free circulating DNA liquid biopsies. [ 6–11 ] However, electrochemical methods that use certain types of electrodes have limitations. Specifically, these electrodes must be composed of noble metals, and have complex fabrication processes.…”

“…[1][2][3][4][5] The use of electrokinetic systems enables the precise control of DNA molecules, which is crucial for systematic DNA memory processes, DNA origami manipulation, and cell-free circulating DNA liquid biopsies. [6][7][8][9][10][11] However, electrochemical methods that use certain types of highly conductive 3D structure. Shaped LMs in microfluidics have low vapor pressure and mechanical stability when the surface of the material is oxidized in air or water.…”

Rapid purification and multiparametric characterization of circulating small extracellular vesicles utilizing a label-free lab-on-a-chip device

“…Microfluidic devices target physical properties at the microscale level and enable rapid and high throughput isolation of sEVs by employing external forces. Electrokinetic based microfluidics are one set of such devices that isolate sEVs based on external electrical forces without the need to tag or label molecules of interest 21 , 22 . The dielectrophoresis (DEP) phenomenon can achieve specific isolation based on the dielectric properties and size distribution of sEVs under a non-uniform electric field, in a rapid and label-free manner.…”