Digital microfluidics: A promising technique for biochemical applications

doi:10.1007/s11465-017-0460-z

Front. Mech. Eng.

2017, Vol. 12

Issue (4) : 510-525 https://doi.org/10.1007/s11465-017-0460-z

REVIEW ARTICLE

Digital microfluidics: A promising technique for biochemical applications

He WANG^1,², Liguo CHEN¹(

), Lining SUN¹

¹. Robotics and Microsystems Center, Soochow University, Soochow 215006, China
². School of Mechanical Engineering, Henan University of Engineering, Zhengzhou 451191, China

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Abstract

Digital microfluidics (DMF) is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DMF, discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by applying electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields (e.g., chemistry, biology, medicine, and environment). This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.

Keywords digital microfluidics electrowetting on dielectric discrete droplet biochemistry

Corresponding Author(s): Liguo CHEN

Just Accepted Date: 07 June 2017 Online First Date: 27 July 2017 Issue Date: 31 October 2017

Cite this article:

He WANG,Liguo CHEN,Lining SUN. Digital microfluidics: A promising technique for biochemical applications[J]. Front. Mech. Eng., 2017, 12(4): 510-525.

URL:

https://academic.hep.com.cn/fme/EN/10.1007/s11465-017-0460-z
https://academic.hep.com.cn/fme/EN/Y2017/V12/I4/510

Fig.1 DMF: (a) Side-view schematics of the parallel-plate (left) and single-plate (right) DMF devices; (b) photos of the TCC and L-junction reservoirs; (c) schematics of the twin-plate electrowetting configuration; (d) photo (upper left) of the fabricated single-plate electrowetting-on-dielectric device with island-ground electrode (IG-SEWOD) device, snapshots (lower left) of the droplet transport, and comparison of the droplet dynamic properties in the X-direction (upper right) and Y-direction (lower right) transport between the IG-SEWOD and floating EWOD device; (e) photo (left) of the inkjet-printed paper chip, and a series of frames (right) from a movie (I to VIII) that depicts the mixing process of the three droplets; (f) isometric-view schematic (left) and photo (right) of the inkjet printed, roll-coated paper DMF chip, as well as photo (middle) of a roll of inkjet-printed bottom plate placed on a mini roll coater to coat a layer of Cyanoresin CR-S cyanoethyl pullulan as the dielectric layer

Fig.2 DMF applications in chemical/enzymatic reactions and immunoassays. (a) Top-view (upper) and side-view (lower) schematics of the SPME-DMF interface; (b) photo (left) that overlooks the EWOD radiosynthesis chip positioned below a pivoting mirror, which directs light to either the video camera or Cerenkov camera inside a light tight box of a Cerenkov imaging system, schematic (top right) of the faster mixing process through the circulating-actuation of EWOD electrodes; and Cerenkov image (bottom right) after 30 s of the mixing based on EWOD actuation; (c) top-view schematic (left) of femtoliter droplets printed inside hydrophilic patches after a mother droplet moves across micro-patches, and scanning electron microscope image (right) of single MOF crystal arrays formed by the DMF technique; (d) schematic (top left) of the three-electrode design with two different sizes for the micromagnetic particle extraction, measured particle loss rates (top middle) with different starting particle numbers and comparison (top right) of the washing efficiency in the case of two different electrode-area ratios; and images (bottom) of a mother droplet that split into two daughter droplets with different sizes by the improved double-side EW method

Fig.3 Cell-based applications in DMF. (a) Frames (1)–(6) of a movie (left) show the driving protocol for generating a droplet with 150 mM (1 mM=1 mmol/L) IL. Repeating Frames (2)–(5) for the other IL concentrations to generate four droplets with different ionic liquid concentrations at 0, 37.5, 75, or 150 mM (Frame 6). Each droplet first captured a single cell and was then actuated into their respective culture regions. Photo (right) of a single S. cerevisiae cell incubated at four different concentrations of [C₂mim][Cl]. (b) Photos (upper) of HeLa cells cultured on a hydrophilic region of a DMF device and a photo (inset) of cells on a contradional 96-well plate; photos (lower) of cells that undergo apoptosis before and after two sequential wash steps on the two devices. (c) Photos (upper) of gel discs on a finger (left) and on the DMF device without the upper plate (right); photos of a 3D cell culture: NIH-3T3 cells were cultured in 0.58 wt% agarose gel discs on DMF devices, and imaged through transparent windows on DMF devices utilizing bright field (left), fluorescence (middle) with calcein AM dye, and confocal fluorescence (right) with 4^', 6-diamidino-2-phenylindole (shown in red) and phalloidin (shown in blue) microscopies

Fig.4 DMF applications in DNA-based and protein assays. (a) Photos of SYBR-Green added to double-stranded DNA and generated fluorescence light; photos (left and right) indicate the optical and fluorescent images, respectively. (b) Overview (left) of a DMF cartridge design, and POP assembly schematics (upper right) of DNA synthesis utilizing DMF. A droplet with a DNA template (gray) was mixed with the assembly droplet 1 (AD1), which contained the primers and assembly mixture to generate a droplet (gray) that contained assembly product 1 (AP1); the AP1 droplet was then mixed in sequence with the assembly droplet 2 (AD2), 3 (AD3), and 4 (AD4), which all contained the primers and assembly mixture until generating the full-length molecule (AP4) 2 (AD2). Scheme (lower right) of in vitro cloning by smPCR on DMF. (c) Top view of the integrated microfludics system and side view of the interface that connects the DMF hub and capillary (left); sequence of frames (right) from a movie that describes the automated library preparation process for a sample that contains human gDNA from peripheral blood mononuclear cells. (d) A series of images from a video (left) and schematic (right) that show the digestion process for a proteomic sample on a hydrogel disc microreactor (2 mm in diameter)

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