Mixing in microfluidic devices and enhancement methods

Abstract

Mixing in microfluidic devices presents a challenge due to laminar flows in microchannels, which result from low Reynolds numbers determined by the channel's hydraulic diameter, flow velocity, and solution's kinetic viscosity. To address this challenge, novel methods of mixing enhancement within microfluidic devices have been explored for a variety of applications. Passive mixing methods have been created, including those using ridges or slanted wells within the microchannels, as well as their variations with improved performance by varying geometry and patterns, by changing the properties of channel surfaces, and by optimization via simulations. In addition, active mixing methods including microstirrers, acoustic mixers, and flow pulsation have been investigated and integrated into microfluidic devices to enhance mixing in a more controllable manner. In general, passive mixers are easy to integrate, but difficult to control externally by users after fabrication. Active mixers usually take efforts to integrate within a device and they require external components (e.g. power sources) to operate. However, they can be controlled by users to a certain degree for tuned mixing. In this article, we provide a general overview of a number of passive and active mixers, discuss their advantages and disadvantages, and make suggestions on choosing a mixing method for a specific need as well as advocate possible integration of key elements of passive and active mixers to harness the advantages of both types.

Keywords: flow controls; microfluidics; micromixers; mixing; review.

Figure 1

(a) Images and simulated predictions for concentration contour at the entry (left) and exit (right) of a microfluidic channel at a flow rate of 2 ml min⁻¹. The degree of mixing is minimal because the mixing is relying on diffusion alone (adapted from [27] with permission). (b) Scanning electron micrograph (SEM) of a mixer consisting of 2 × 15 interdigital channels with corrugated walls (adapted from [28] with kind permission from Springer Science and Business Media). (c) Diagram of serpentine laminating micromixer (adapted from [29] with permission from The Royal Society of Chemistry).

Figure 2

(a) Configuration of the experimental setup and image of a channel with a series of slanted wells. (b) Image of a smooth channel. (c), (d) Fluorescence image of electroosmotic flow of the corresponding channels in (a) and (b). (e) Fluorescence image for electroosmotic flow past an optimized mixer at a high flow rate (0.81 cm s⁻¹). These figures are adapted from [37] with permission.

Figure 3

(a) Schematic diagram of one-and-a-half cycles of the SHM. A mixing cycle is composed of two sequential regions of ridges; the direction of asymmetry of the herringbones switches with respect to the centerline of the channel from one region to the next. At the bottom are confocal micrographs of vertical cross sections of a channel (from [7]. Reprinted with permission from AAAS). (b) (left) Illustration of isotropic etching and ridges obtained from judicious designs and isotropic etching; (right) SEM picture of a ridged channel in a microfluidic device made from a cyclic olefin copolymer. The scaling bar is 200 µm (adapted with permission from [42]. Copyright 2007 American Chemical Society).

Figure 4

(a) Visualization of mixing enhancement within liquid plugs and downstream separation of the liquid and gas phases. (b) Streamlines and visualization of recirculation within liquid plugs in straight channels. (c) Streamlines and visualization of recirculation within liquid plugs at the bends of winding channels. These figures were adapted with permission from [56]. Copyright 2005 American Chemical Society.

Figure 5

(a) Schematic diagram combining surface hydrophobicity and microridges, allowing water to stand away from the solid surface. (b) Improvement in the degree of mixing by hydrophobic microridges (solid squares) in comparison with hydrophilic microridges (open squares) and smooth surface (solid diamonds). Reprinted with permission from [61]. Copyright 2007 American Physical Society.

Figure 6

(a) Fluorescence micrograph of mixing chamber without magnetic particles. No mixing enhancement occurs and the mixing relies solely on diffusion. (b) Fluorescence micrograph of mixing chamber with non-rotating magnetic particles. Mixing is enhanced but not complete using this configuration. (c) Fluorescence micrograph of mixing chamber with rotating magnetic particles. Efficient mixing is observed using this configuration. These figures are adapted from [68] with permission from the Royal Society of Chemistry. Copyright 2009 Royal Society of Chemistry. (d) Mixing enhancements observed over time when using magnetically actuated artificial cilia for three separate cilia trajectories. Adapted from [70] with permission from the Royal Society of Chemistry. Copyright 2013 Royal Society of Chemistry.

Figure 7

(a) Two tapered IDT (TIDT) exciting SAWs in x and y directions. An envelope controller runs predefined programs modulating the amplitude of the SAW arbitrarily. When operating in dual-jet mode, TIDT I works at constant power (solid line), and the power of TIDT II is modulated (dashed line). (b) Diagram of a SAW mixer. Reprinted figures with permission from [72]. Copyright 2008 American Physical Society. (c) A bubble is trapped inside the horseshoe structure. No mixing effect was observed in the absence of acoustic waves. (d) Homogenized mixing of water and fluorescent dye in presence of acoustic waves. The flow is from the right to the left (adapted from [73] with permission from The Royal Society of Chemistry). Copyright 2009 Royal Society of Chemistry.

Figure 8

(a) Two inlets indicated by inward arrows have pulsation flows while one outlet is marked by an outward arrow. Pulsation is indicated by the graph next to each inlet, showing the mean velocity as a function of time. The phase difference is 90° between flows at two inlets. Contour plots show concentration of the liquid at half the depth of the channel and at 0.5 mm downstream of the confluence (adapted with permission from [80]. Copyright 2004 American Chemical Society). (b) Experimental results of mixing by perturbed flows generated using one pair of side channels (adapted from [81] with permission. © 2003 IOP Publishing.

Figure 9

Pictures of a device with schematic drawing representing components of the device. During operation, blue food dye from inlet port 1 and isopropyl alcohol from inlet port 2 mix at point E. The nozzle-diffuser-based bubble pump generates oscillatory flows intrinsically, inducing mixing effects (adapted from [85] with permission). Copyright 2002 Elsevier.

Figure 10

(a) Flow profile generated by the ac electrokinetic mixer and the charge accumulation on the surface of the electrodes. (b) Schematic of the micromixer device and flow profile generation. (c) Laminar flow of two fluids in a microfluidic channel with (bottom) and without (top) the ac and dc voltage components applied. A clear enhancement of the stream mixing can be seen over small distances when the voltages are applied. These figures were adapted from [88] with permission. Copyright 2009 Royal Society of Chemistry.