Abstract Organic phase enzyme electrodes (OPEEs) offer new possibilities both for the design of biosensors for use in organic solvents and in the construction of devices incorporating an organic phase for use with aqueous samples. The advantages that accrue from performing biocatalytic and electrochemical reactions in non-aqueous systems are discussed in relation to possible applications in medicine, pharmaceuticals, petrochemicals, the food industry, environmental monitoring and defence. This critical but speculative review considers the detailed implications of operating enzyme electrodes in organic solvents and briefly examines the broader issues of optical, calorimetric and piezoelectric transduction coupled with both catalytic and affinity systems, such as nucleic acid probes and antibodies.

Organic phase enzyme electrodes

Dielectrophoresis can potentially be used as an efficient trapping tool in the fabrication of molecular devices. For nanoscale objects, however, the Brownian motion poses a challenge. We show that the use of carbon nanotube electrodes makes it possible to apply relatively low trapping voltages and still achieve high enough field gradients for trapping nanoscale objects, e.g., single molecules. We compare the efficiency and other characteristics of dielectrophoresis between carbon nanotube electrodes and lithographically fabricated metallic electrodes, in the case of trapping nanoscale DNA molecules. The results are analyzed using finite element method simulations and reveal information about the frequency dependent polarizability of DNA.

https://arxiv.org/pdf/cond-mat/0607446.pdf

Carbon Nanotubes as Electrodes for Dielectrophoresis of DNA

Dielectrophoretically driven microfluidic devices have demonstrated great applicability in biomedical engineering, diagnostic medicine, and biological research. One of the potential fields of application for this technology is in point-of-care (POC) devices, ideally allowing for portable, fully integrated, easy to use, low-cost diagnostic platforms. Two main approaches exist to induce dielectrophoresis (DEP) on suspended particles, that is, electrode-based DEP and insulator-based DEP, each featuring different advantages and disadvantages. However, a shared concern lies in the input voltage used to generate the electric field necessary for DEP to take place. Therefore, input voltage can determine portability of a microfluidic device. This review outlines the recent advances in reducing stimulation voltage requirements in DEP-driven microfluidics.

Toward low-voltage dielectrophoresis-based microfluidic systems: A review

Abstract Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized. 

/pdf/tumor-buster-where-will-the-car-t-cell-therapy-missile-go-2dx4nk5i.pdf

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Insulator-based dielectrophoretic (iDEP) trapping, separating, and concentrating nanoscale objects is carried out using a non-metal, unbiased, mobile tip acing as a tweezers. The spatial control and manipulation of fluorescently-labeled polystyrene particles and DNA were performed to demonstrate the feasibility of the iDEP tweezers. Frequency-dependent iDEP tweezers' strength and polarity were quantitatively determined using two theoretical approaches to DNA, which resulted in a factor of 2 ~ 40 differences between them. In either approach, the strength of iDEP was at least 4-order of magnitude stronger than the thermal force, indicating iDEP was a dominant force for trapping, holding, and separating DNA. The trapping strength and volume of the iDEP tweezers were also determined, which further supports direct capture and manipulation of DNA at the tip end.

Selective Manipulation of Biomolecules with Insulator-Based Dielectrophoretic Tweezers

Design of Micro‐interdigitated Electrodes and Detailed Impedance Data Analysis for Label‐free Biomarker Quantification

https://iopscience.iop.org/article/10.1088/1361-6463/abc2f3/pdf

Dielectrophoretic High Purity Isolation of Primary T-cells in Samples Contaminated with Leukemia Cells, for Biomanufacturing of Therapeutic CAR T-cells

The detection and quantification of nucleic acid and proteomic biomarkers in bodily fluids is a critical part of many medical screening and diagnoses. However, majority of the current detection platforms are not ideal for routine, rapid, and low-cost testing in point-of-care settings. To address this issue, we developed a concept for a disposable universal point-of-care biosensor that can detect and quantify nucleic acid and proteomic biomarkers in diluted serum samples. The central tenet of sensing is the use of dielectrophoresis, electrothermal effects, and thermophoresis to selectively and rapidly isolate the biomarkers of interest in electrodes and then quantify using electrical impedance. When the sensor was applied to quantify microRNA and antigen biomarker molecules directly in diluted serum samples, it produced a LOD values in the fM range and sensitivity values from 1012 to 1015 Ω/M with a 30 min assay time and assay cost of less than $50 per assay.

Integrated dielectrophoretic and impedimetric biosensor provides a template for universal biomarker sensing in clinical samples

Dielectrophoresis is a well-understood phenomenon that has been widely utilized in biomedical applications. Recent advancements in miniaturization have contributed to the development of dielectrophoretic-based devices for a wide variety of biomedical applications. In particular, the integration of dielectrophoresis with microfluidics, fluorescence, and electrical impedance has produced devices and techniques that are attractive for screening and diagnosing diseases. This review article summarizes the recent utility of dielectrophoresis in assays of biomarker detection. Common screening and diagnostic biomarkers, such as cellular, protein, and nucleic acid, are discussed. Finally, the potential use of recent developments in machine learning approaches toward improving biomarker detection performance is discussed. This review article will be useful for researchers interested in the recent utility of dielectrophoresis in the detection of biomarkers and for those developing new devices to address current gaps in dielectrophoretic biomarker detection.

Vidura Jayasooriya

Papers

Selective Manipulation of Biomolecules with Insulator-Based Dielectrophoretic Tweezers

Design of Micro‐interdigitated Electrodes and Detailed Impedance Data Analysis for Label‐free Biomarker Quantification

Dielectrophoretic High Purity Isolation of Primary T-cells in Samples Contaminated with Leukemia Cells, for Biomanufacturing of Therapeutic CAR T-cells

Integrated dielectrophoretic and impedimetric biosensor provides a template for universal biomarker sensing in clinical samples

Recent advances in dielectrophoresis toward biomarker detection: A summary of studies published between 2014 and 2021.