Passivated‐electrode insulator‐based dielectrophoretic separation of heterogeneous cell mixtures

Kikkeri, Kruthika; Kerr, Bethany A.; Bertke, Andrea S.; Strobl, Jeannine S.; Agah, Masoud

doi:10.1002/jssc.201900553

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…Although nanoparticle isolation through the incorporation of electric fields has shown promise, exosome isolation using this technique is still challenging. Direct contact between sample solution and the electrodes as well as high operational voltage required in some devices generates excessive heat that could result in the denaturation of biological components. − It should also be noted that applied electrical field influences the movement of not only exosomes but also all other nanoparticles, thereby extracting EVs copurified with impurities such as protein aggregates. Obviously, a pure isolation of EVs using this approach needs a highly controlled flow velocity and voltage magnitude to improve the separation efficiency.…”

Section: Label-free Microfluidic Methods For Exosome Isolationmentioning

confidence: 99%

Label-Free Isolation of Exosomes Using Microfluidic Technologies

2021

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Exosomes are cell-derived structures packaged with lipids, proteins, and nucleic acids. They exist in diverse bodily fluids and are involved in physiological and pathological processes. Although their potential for clinical application as diagnostic and therapeutic tools has been revealed, a huge bottleneck impeding the development of applications in the rapidly burgeoning field of exosome research is an inability to efficiently isolate pure exosomes from other unwanted components present in bodily fluids. To date, several approaches have been proposed and investigated for exosome separation, with the leading candidate being microfluidic technology due to its relative simplicity, costeffectiveness, precise and fast processing at the microscale, and amenability to automation. Notably, avoiding the need for exosome labeling represents a significant advance in terms of process simplicity, time, and cost as well as protecting the biological activities of exosomes. Despite the exciting progress in microfluidic strategies for exosome isolation and the countless benefits of label-free approaches for clinical applications, current microfluidic platforms for isolation of exosomes are still facing a series of problems and challenges that prevent their use for clinical sample processing. This review focuses on the recent microfluidic platforms developed for labelfree isolation of exosomes including those based on sieving, deterministic lateral displacement, field flow, and pinched flow fractionation as well as viscoelastic, acoustic, inertial, electrical, and centrifugal forces. Further, we discuss advantages and disadvantages of these strategies with highlights of current challenges and outlook of label-free microfluidics toward the clinical utility of exosomes.

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Section: Label-free Microfluidic Methods For Exosome Isolationmentioning

confidence: 99%

Label-Free Isolation of Exosomes Using Microfluidic Technologies

2021

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“…Kikkeri et al created and incorporated a passivated-electrode insulator-based DEP microchip to fabricate a separation channel that would expose cells to the DEP forces as they travel through the microchip (Figure 3d). 128 By incorporating multiple winding rows with several nonuniform structures into the sidewalls of the microchip, they were able to produce a high electric field gradient and a high locally generated DEP force for safely separating cancer cells spiked in whole blood based on their morphology with 90% separation efficiency. The iDEP electrodes can also be externally placed in the inlets and outlets.…”

Section: Categories Of Microfluidic Dep Devicesmentioning

confidence: 99%

Methods of Generating Dielectrophoretic Force for Microfluidic Manipulation of Bioparticles

Kwizera

Sun

White

et al. 2021

ACS Biomater. Sci. Eng.

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Manipulation of microscale bioparticles including living cells is of great significance to the broad bioengineering and biotechnology fields. Dielectrophoresis (DEP), which is defined as the interactions between dielectric particles and the electric field, is one of the most widely used techniques for the manipulation of bioparticles including cell separation, sorting, and trapping. Bioparticles experience a DEP force if they have a different polarization from the surrounding media in an electric field that is nonuniform in terms of the intensity and/or phase of the electric field. A comprehensive literature survey shows that the DEP-based microfluidic devices for manipulating bioparticles can be categorized according to the methods of creating the nonuniformity via patterned microchannels, electrodes, and media to generate the DEP force. These methods together with the theory of DEP force generation are described in this review, to provide a summary of the methods and materials that have been used to manipulate various bioparticles for various specific biological outcomes. Further developments of DEP-based technologies include identifying materials that better integrate with electrodes than current popular materials (silicone/glass) and improving the performance of DEP manipulation of bioparticles by combining it with other methods of handling bioparticles. Collectively, DEP-based microfluidic manipulation of bioparticles holds great potential for various biomedical applications.

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“…Because different cell types have different dielectric properties, DEP can be used in the isolation of particular cell types of interest from heterogeneous cellular populations. DEP can also be used to separate cells and aggregates of different sizes within homogenous cellular populations [102][103][104][105].…”

Section: Dielectrophoresismentioning

confidence: 99%

Preparation of Tissues and Heterogeneous Cellular Samples for Single-Cell Analysis

Welch¹,

Tripathi²

2021

Sample Preparation Techniques for Chemical Analysis

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While sample preparation techniques for the chemical and biochemical analysis of tissues are fairly well advanced, the preparation of complex, heterogenous samples for single-cell analysis can be difficult and challenging. Nevertheless, there is growing interest in preparing complex cellular samples, particularly tissues, for analysis via single-cell resolution techniques such as single-cell sequencing or flow cytometry. Recent microfluidic tissue dissociation approaches have helped to expedite the preparation of single cells from tissues through the use of optimized, controlled mechanical forces. Cell sorting and selective cellular recovery from heterogenous samples have also gained traction in biosensors, microfluidic systems, and other diagnostic devices. Together, these recent developments in tissue disaggregation and targeted cellular retrieval have contributed to the development of increasingly streamlined sample preparation workflows for single-cell analysis technologies, which minimize equipment requirements, enable lower processing times and costs, and pave the way for high-throughput, automated technologies. In this chapter, we survey recent developments and emerging trends in this field.

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Passivated‐electrode insulator‐based dielectrophoretic separation of heterogeneous cell mixtures

Cited by 16 publications

References 39 publications

Label-Free Isolation of Exosomes Using Microfluidic Technologies

Label-Free Isolation of Exosomes Using Microfluidic Technologies

Methods of Generating Dielectrophoretic Force for Microfluidic Manipulation of Bioparticles

Preparation of Tissues and Heterogeneous Cellular Samples for Single-Cell Analysis

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