Low‐cost, high‐throughput and rapid‐prototyped 3D‐integrated dielectrophoretic channels for continuous cell enrichment and separation

Abstract

Microfluidic devices for dielectrophoretic cell separation are typically designed and constructed using microfabrication methods in a clean room, requiring time and expense. In this paper, we describe a novel alternative approach to microfluidic device manufacture, using chips cut from conductor–insulator laminates using a cutter plotter. This allows the manufacture of microchannel devices with micron‐scale electrodes along every wall. Fabrication uses a conventional desktop cutter plotter, and requires no chemicals, masks or clean‐room access; functional fluidic devices can be designed and constructed within a couple of hours at negligible cost. As an example, we demonstrate the construction of a continuous dielectrophoretic cell separator capable of enriching yeast cells to 80% purity at 10 000 cells/s.

Integrated Microfluidics for Single‐Cell Separation and On‐Chip Analysis: Novel Applications and Recent Advances

“…[ 238 ] Recently, Faraghat et al fabricated a DEP‐based microfluidic platform by structuring conductor–insulator laminates via a desktop cutting plotter. [ 239 ] This system could be used for the high‐throughput continuous separation of yeast cells in a low‐cost manner, without the need for wet lab facilities for the production of the platforms.…”

“…• Label-free, contact-free separation • Separation based on intrinsic dielectric polarizability [21] • Unique electrical characteristics of different cell types identifiable [21] • Easy integration as microelectrode integration into microfluidic systems well-established • Wireless operation possible via bipolar electrode architecture [42,132,252,253] • DEP force acting on a cell/particle significantly varied as a function of distance away from an electrode edge [21] • Adverse effects on samples due to Joule heating when high electric field strength is required [25] • Possible degradation of the electrode and the nearby biological samples due to the electrochemical activity at the electrode-buffer interface [25,26,153] • Dependence on the electrical properties of the medium, which may necessitate specific buffer conditions that are optimal for cells [26,28,42,201] • Besides trapping, controlled transport and motion of cells and particles based on DEP [42,43] • Use of cheaper materials and easier fabrication methods [238,239,250] • Combination with other separation methods [251] Magnetophoresis • Well-established magnetic cell labeling [21] • Magnetic particle kits commercially available • Magnetic particle properties do not degrade and are commonly not affected by chemistry [21] • No significant magnetic noise usually present to interfere with cell/particle manipulation [21] • Relatively little heat generation [53] • Magnetic fields can penetrate most microfluidic materials [53] • Most often label-based • Biocompatibility of some magnetic particles not thoroughly studied [201] • Biocompatibility of ferrofluids for label-free magnetophoresis a key challenge [46] • Generation of controlled magnetic forces not straightforward [21] • Sorting efficiency limited by the strength of the magnetic field and the magnetic properties of the medium and particles…”

Dielectrophoretic Particle Chromatography: From Batch Processing to Semi-Continuous High-Throughput Separation

“…When a polarizable particle is subjected to an inhomogeneous electric field, a movement can be observed, which is called dielectrophoresis (DEP) [6]. Dielectrophoresis is currently mostly used to manipulate or analyze biological particles [7] such as cells [8][9][10], DNA [11] or proteins [12,13]. Here, microfluidic setups are mostly used as high electric field gradients required to generate sufficient DEP force.…”

Optimized hybrid dielectrophoretic microchip for separation of bioparticles

“…Although the separators can be evaluated by their simplicity, throughput, purity, and other factors [13], generally, they are classified into two types, active and passive separators [14]. Active separators, such as ultrasound [3,[15][16][17][18][19], optical manipulation [20][21][22], dielectrophoresis (DEP) [23][24][25][26][27][28], magnetophoresis [29,30], and capillary and free-flow electrophoresis [31][32][33][34], involve external forces for separating particles resulting in a controlled separation and high purity [35,36]. However, the heat produced by the electric field in electrophoretic-based separators may harm some cells [35], which has hindered the applications of this type of active separator.…”