A critical review on the fabrication techniques that can enable higher throughput in dielectrophoresis devices

Abstract

The sorting of targeted cells in a sample is a cornerstone of healthcare diagnostics and therapeutics. This work focuses on the use of dielectrophoresis for the selective sorting of targeted bioparticles in a sample and how the lack of throughput has been one important practical challenge to its widespread practical implementation. Increasing the cross‐sectional area of a channel can lead to higher flow rates and thus the capability to process a larger sample volume per unit of time. However, the required electric field gradient that is generated by polarized electrodes drastically decreases as one moves away from the electrodes. Hence, the scaling up of the channel cross section must be done asymmetrically. One desires a channel aspect ratio AR = height/width that is much smaller or much larger than 1. Since reducing footprint of the DEP device is important to ensure affordability, the use of channels with AR ≫ 1 is desired. This creates the challenge to fabricate electrodes on the sidewalls of multiple channels with AR ≫ 1, or a channel embedding an array of electrodes with a gap in between them with AR ≫ 1. This critical review first details the motivation for using three‐dimensional (3D) DEP devices to improve throughput and then describes selected techniques that have been used to fabricate them. Techniques include electrodeposition, deep etching, thick‐film photolithography, and co‐fabrication. Electrode materials addressed include metals, silicon, carbon, PDMS‐based composites as well as conductive polymers and fluids.

High‐throughput dielectrophoretic separator based on printed circuit boards

“…Most DEP separators are microfluidic devices and therefore handle volume flows in the $$\umu\mathrm{L}/\mathrm{h}$$ or lower ml/h range [20, 28, 29]. For highly valuable products such as proteins or cells, this is sufficient and can be considered as high throughput [7, 30, 31].…”

“…These cannot only be utilized as electrodes but also as master molds for replica molding in microfluidics [42]. While clean rooms offer the opportunity to create electrodes with small width and spacing or three‐dimensional structures that are required for highly sensitive separators and sensors [29, 43], commercially manufactured PCB are cheap and can be obtained without access to a clean room. Further, PCB can be produced with large surface areas (e.g., 46 × 61 cm [40]), while maintaining small enough electrode spacing for many applications (minimum feature size around $$100\,\umu$$m) [40, 41].…”

“…During device scale up, it is therefore important to keep the gradient of the electric field high, so that DEP is the dominant force in the separator. In microfluidic separators the gradient is often generated by using either interdigitated electrodes (IDE) [11,29,33,34] or via disturbing an otherwise homogeneous electric field by adding insulating structures into the device [10,35,36]. These two approaches are referred to as electrode-based DEP (eDEP) and insulator-based DEP (iDEP).…”

Evaluating carbon-electrode dielectrophoresis under the ASSURED criteria

“…Such different behaviors are what enable the spatiotemporal manipulation of target cells that can lead to their identification and separation from a background. Over the years, several techniques have emerged to implement the electric field gradient necessary for DEP as previously reviewed by one of us ( 22 , 23 ). This article particularly focuses on carbon-electrode dielectrophoresis (CarbonDEP), mainly due to the relatively inexpensive fabrication process, the robust and electrochemical inert nature of carbon electrodes, and the potential for high throughput sample processing.…”

Effects of 3D electrodes arrangement in a novel AC electroosmotic micropump: Numerical modeling and experimental validation

“…Recently, microfabrication technology has simplified the fabrication of microfluidic devices using polymers as a base material that has been utilized in various methods such as soft lithography, injection molding, and so on. [10,11].…”