Defining Cell Cluster Size by Dielectrophoretic Capture at an Array of Wireless Electrodes of Several Distinct Lengths

Abstract

Clusters of biological cells play an important role in normal and disease states, such as in the release of insulin from pancreatic islets and in the enhanced spread of cancer by clusters of circulating tumor cells. We report a method to pattern cells into clusters having sizes correlated to the dimensions of each electrode in an array of wireless bipolar electrodes (BPEs). The cells are captured by dielectrophoresis (DEP), which confers selectivity, and patterns cells without the need for physical barriers or adhesive interactions that can alter cell function. Our findings demonstrate that this approach readily achieves fine control of cell cluster size over a broader range set by other experimental parameters. These parameters include the magnitude of the voltage applied externally to drive capture at the BPE array, the rate of fluid flow, and the time allowed for DEP-based cell capture. Therefore, the reported method is anticipated to allow the influence of cluster size on cell function to be more fully investigated.

Recent Advancements in Bipolar Electrochemical Methods of Analysis

“…[5][6][7][8][9][10] Their ability to modulate local electric fields lends them to the manipulation of cells and to the enrichment and separation of analytes. [11][12][13][14][15][16][17] And finally, by virtue of the polar and often graded profile of the interfacial potential across BPEs, they provide a platform for synthesis of Janus particles, useful as sensors and as microswimmers, [18][19][20][21][22] and other materials with compositional gradients. 23,24 BPEs are particularly well-suited to analytical challenges that demand multiplexing or amenability to point-of-need (PON) application because even large arrays of BPEs can be controlled with simple equipment, yet yield quantitative information about a system.…”

“…Our group has also demonstrated that BPE length and shape, along with other variables, can be used to control the number of cells captured at BPE tips. 11 For these reasons, BPEs provide a convenient means by which to define parallel or serial dielectrophoretic capture points.…”

“…The goal of this review is to provide an overview of the advancements made in the field of bipolar electrochemistry over the past 2 years, with an emphasis on analysis. Bipolar electrodes (BPEs) are versatile, and in electroanalysis, they have been used extensively to screen electrocatalysts − and to sense biomarkers. − Their ability to modulate local electric fields lends them to the manipulation of cells and to the enrichment and separation of analytes. − Finally, by virtue of the polar and often graded profile of the interfacial potential across BPEs, they provide a platform for synthesis of Janus particles, useful as sensors and as microswimmers − and other materials with compositional gradients. , BPEs are particularly well-suited to analytical challenges that demand multiplexing or amenability to point-of-need (PON) application because even large arrays of BPEs can be controlled with simple equipment yet yield quantitative information about a system. In this review, we discuss recent progress in reactions that transduce current to a visible signal, sensing mechanisms, bipolar electrochemical cell design, integration of bipolar electrochemistry with spectroscopic techniques, BPEs at the nanoscale, and the application of BPEs to electrokinetics and materials preparation.…”

Redox Cycling at an Array of Interdigitated Bipolar Electrodes for Enhanced Sensitivity in Biosensing**

“…BPEs have found application in many areas including electrochemical imaging, 1 electrokinetic separations, 2-5 materials synthesis, 6,7 electrocatalyst screening, 8 micromotors, 9,10 singlecell analysis, [11][12][13] visual voltammetry, 14,15 point-of-care sensing 16 and biosensing. 17 Recent advancements in bipolar electrochemical methods of analysis are discussed in a recent review by Rahn et al 18 A BPE comprises a conductor immersed in an electrolyte solution.…”

Editorial for the Special Issue on AC Electrokinetics in Microfluidic Devices

“…Lo and Lei [4] showed a simple flow-through device for continuous and massive lysis of cells via electricity. Banovetz et al [5] reported a method that uses an array of wireless bipolar electrodes to pattern cells into clusters.…”