Utilization of Interdigitated Microelectrodes and Dielectrophoresis for Biosensing, Bio Molecule Manipulation and Biomanufacturing Therapeutic Cells
Jayasooriya, Vidura Dhananjaya
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Microelectrode arrays (MEA) and microfluidic systems are two of the most used technologies in Lab-on-a-chip (LOC) applications. These integrated and miniaturized systems are said to offer significant advantages in medical applications due to their high sensitivity, high throughput, lower material consumption, low cost, and enhanced Spatio-temporal control. Further, the physical laws at the micro-scale offer certain advantages in terms of the control of physical, biological and chemical properties in diagnostics or therapeutics at the cellular or molecular level. Moreover, these platforms are portable and can be easily designed for point-of-care diagnostics. Unfortunately, among various microelectrode and microfluidic technologies available today, only a few have been proven to be useful in clinical applications. One of the reasons behind this issue is the lack of efficient and sensitive methods to integrate the handling of biological materials in microfluidic devices. This has created a gap between real-world clinical applications and this emerging technology. To address this issue, in this work, externally applied electric fields have integrated with MEA and microfluidics systems. Moreover, this work has centered on dielectrophoresis, which is a result of the interaction between biological materials (e.g., DNA, RNA and cells) and external electric fields. Dielectrophoretic force (DEP force) was used to selectively manipulate biological materials within microfluidics devices. This capability opened up avenues for biosensing and biomanufacturing. This work was organized in the following manner: first, we investigated the production of DEP force, selectivity and limits. Second, the new knowledge learned from dielectrophoresis experiments was used to develop novel biomarker sensing technologies or sensors. Third, dielectrophoretic cell purification methods needed for the production of safe chimeric antigen receptor (CAR) T-cells for treating cancer, was investigated. Finally, a novel method for the manufacturing of viral vector-free CAR T-cells was developed. Results from these studies have shown that integration dielectrophoresis with MEA and microfluidics provides a new class of tools for unmet needs in clinical applications. Finally, fundamental studies on dielectrophoresis provide new insights into its origin and limits. Developed technologies could be used in clinical applications after validation.