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.
Highlights
We demonstrate a method for patterning biological cells that achieves control over the size of small cell clusters (2–12 cells) by their dielectrophoretic capture at an array of wireless bipolar electrodes (BPEs) having several distinct lengths (Scheme 1a,b)
Control over Cluster Size at Higher Voltage, Flow Rate, and Duration based on the results presented in the previous subsections, we hypothesized that a greater dependence of cluster size on BPE length could be achieved at a higher flow rate and voltage
We have demonstrated that cell cluster size is dependent on BPE length, and varies moreIsnteceopnlcyluwsihoenr,ewFedrhaagvperedseemntosnastcrhataeldlenthgaet tcoelFl dcrlaugsttehrastidzeisitsridbeupteesndtheentporonbBaPbEililteyngotfhc,eallncdavpaturirees amt oeraechsteBePpElylewnhgetrhe iFndrtahg epraersreanyt.s Ta hchisalBlePnEg-eletnogFthdraegfftheactt disisltersibsuptreosntohue npcreodbatbhialintythoaf tcealclhciaepvteudrebayt aelatecrhinBgPtEhleeanpgpthlieindtvhoeltaargreay(∆
Summary
We demonstrate a method for patterning biological cells that achieves control over the size of small cell clusters (2–12 cells) by their dielectrophoretic capture at an array of wireless bipolar electrodes (BPEs) having several distinct lengths (Scheme 1a,b). We show that capture force, and cluster size, is positively correlated with BPE length This relationship arises from an increase in the electrical potential difference across the solution in contact with each BPE (∆UBPE) on its length (Scheme 1c). This finding is significant because control over cluster size is achieved without physical barriers or surfaces with pre-patterned biomolecules, and the cluster size is readily tunable via voltage and fluid flow rate. We describe the dependence of the number of cells captured in each cluster on BPE length, the magnitude and duration of the voltage applied externally to drive DEP-based capture at the array, and the flow rate of the cell solution
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