Author: Rabia Rana Atlan, University of Ankara, Department of Biomedical Engineering
Nowadays, microfluidic devices are known as one of the well-designed essential tools for laboratory analyses that takes its origins at the beginning of the 1990s . While this novel technology grows exponentially, it brings along problems such as hard to standardize pumps or valves and controlling the flow of reagents.
Although microfluidic systems have been designed as simple devices, they have difficulty in an interface with a highly expensive unit that involves electronics and programming units . Hence, researchers have developed digital microfluidics as an attractive alternative of lab-on-a-chip systems.
Well, what is digital microfluidics?
Digital Microfluidics (DMF) is a freshly discovered technology that manipulates the reagents in discrete droplets by applying voltage differences between the underlying electrodes as actuator force [3-5]. In these integrated microfluidic devices, the electrodes are coated by a dielectric material, providing movement, mixing, or separation of the droplets from the input reservoirs independently . Device design techniques and considerations, the physics behind it, and applications will be discussed in following sections.
Device Design Techniques & Considerations
The two different configurations of DMF devices are; (1) Parallel-plate (closed sandwich) and single-plate (open top) formats. In closed format, electrodes are aligned as parallel sheets and liquid stays between them. Closed formats can be introduced that while the lower one is assumed as actuation electrode, upper one functions as a ground plate.
In open format devices, the droplets’ manipulation is performed on the same plate which shows both actuation and ground plate properties. Both of these formats have some superiorities over each other. Parallel-plate DMF systems are suitable all drop processes: moving, splitting, merging, and separating from the reservoir. In addition, reliable droplet volume control is ensured by these devices.
On the other side, single-plate systems are not useful at splitting and separating from the reservoir. However, when the resistance to discrete droplet motion decreases, mixing and moving operations get easier [7, 8]. The droplet operations can be achieved through several mechanisms such as electrowetting [7, 9, 10], thermocapillary force [2, 11, 12], dielectrophoresis , etc.
The most common of them is electrowetting (EW). If the electrical potential is applied regularly to the electrode in the system, the discrete droplets are controlled to accomplish operations. If EW design is desired to obtain, it is must to consider the concept of surface tension feature of liquids in the microscale range. When the droplets are placed on a surface, they tend to minimize their surface energy which reforms into spherical shape . The contact angle, formed between the droplet and the surface is changed with the applied potentials. This potential results in changing the contact angle providing the droplet movement. These analyses are based on Young-Lippman equation which is a kind of thermodynamic approaches .
The other significant consideration for any DMF devices is the cost involved in fabrication. Glass and silicon-based materials are most preferred because of their accessibility. Photolithography and etching are the most common fabrication processes of digital lab-on-a-chip (aka DMF) devices. Additionally, time consumption, deficiency of rapid prototyping, and compulsory requirements of clean room conditions should be taken into account while choosing the correct fabrication technique.
Digital Microfluidic Applications in Chemistry
The devices are ideally suited for chemical synthesis because the droplets are able to be operated as individual and manipulable. This idea was assisted first by using organic solvents, ionic liquids, and aqueous surfactant solutions directly in the droplets at 2006 .
When other studies are examined, it was shown that the droplets may be comprised of polymer solutions, micro or nanoparticles, or polymer precursors to yield different chemical reactions. After the first parallel-plate DMF devices were introduced , control of multistep reactions and use of multiple reagents made the operations easier. On the contrary to other microfluidic devices, DMF is the well fit for chemical synthesis although they have yet to be fully discovered.
Digital Microfluidic Applications in Biomedical Engineering
One of the fundamental application of DMF systems is the implementation of biological processes which usually needs the use of highly expensive reagents . In traditional biological analysis methods, contamination risks which are derived from biofouling and excessive sample usage in reactions are the challenges. For instance, biological molecules can stick on the device surface that may make the system useless after a while because of this fouling .
In order to overcome this difficulty in DMF systems, some surface contact-limiting materials such as oil matrix, graphene oxide, etc. were developed. These improvements made DMF systems common for biological applications in the future [19, 20].
Working on DNA characterization techniques is a critical issue in the fields of pharmaceutical or diagnostic researches, or gene-based therapies . Correspondingly, there have been several studies on digital microfluidic DNA manipulation in literature. The key importance is that DNA researches should be performed on a specific amount of samples in numerous format as introduced above.
The most common DNA-based application is PCR (polymerase chain reaction). The indispensable condition is thermal loops to actualize each step in PCR. Chang et al. developed a DMF device which enables to manipulate temperature controlled droplets by using an embedded heater inside the device. As a result, the duration of the test and consumed reagents were reduced by 50-70% . It is possible to increase application examples as cell-based toxicity assays [23, 24], cell culture procedures and analysis [25, 26].
Future Trends & Conclusion
Novel applications with the rapid development of DMF chips will go cheaper and easier to access for clinical laboratories and researchers. When the fabrication techniques are diversified as paper-based DMF systems or automated DMF chips, complications which are arisen from the current devices will be reduced among all related fields.
Although DMF technology is considered highly effective, facilitative, devisable, there have been many question marks in researchers’ mind. One of them is insufficient sources about these systems because of their infancy. Also, the need for microscale apparatus for research, incomprehensible some mechanism must be resolved in the forthcoming times.
On the contrary of all difficulties, DMF researches will be accelerated as a practical solution for complicated problems in the next years. Many laboratories in the field of biology, chemistry, or medicine seem to adopt this new technology in the future.
 Manz A., et al. (1992), doi: 10.1016/0021-9673(92)80293-4
 Fair R.B.J.M. (2007), doi: 10.1007/s10404-007-0161-8
 Abdelgawad M. and A.R.J.A.M. (2009), doi: 10.1002/adma.200802244
 Miller E.M. (2009), doi: 10.1007/s00216-008-2397-x
 Choi K., et al., (2013), doi: 10.1021/ac401847x
 Wang H., et al. (2017), doi: 10.1007/s11465-017-0460-z
 Cho S.K., et al. (2003), doi: 10.1109/JMEMS.2002.807467
 Wang W. and T.B.J.L.o.a.C. Jones, (2015) doi: 10.1039/C5LC00014A
 Pollack M.G., (2001), Duke University.
 Pollack M.G., et al., (2011), doi: 10.1586/erm.11.22
 Nguyen N.-T., et al. (2006), doi: 10.1088/1742-6596/34/1/160
 Grigoriev R.O.J.P.o.f., (2005), doi: 10.1063/1.1850374
 Fan S.-K., et al. (2009), doi: 10.1039/b816535a
 Sukhatme S., et al. (2012), doi: 10.4172/2155-9538.S8-001
 Chatterjee D., et al., (2006), doi: 10.1039/b515566e
 Jebrail M.J., et al., (2010), doi: 10.1002/anie.201001604
 Jebrail M.J. and A.R.J.C.o.i.c.b., (2010), doi: 10.1016/j.cbpa.2010.06.187
 Srinivasan V., et al., (2004), doi: 10.1016/j.aca.2003.12.030
 Perry G., et al., (2012), doi: 10.1039/c2lc21279j
 Jebrail M.J., et al., (2012), doi: 10.1039/C2LC40318H.
 Choi, K., et al., (2012), doi: 10.1146/annurev-anchem-062011-143028
 Chang Y.-H., et al., (2006), doi: 10.1007/s10544-006-8171-y
 Barbulovic-Nad I., et al.,(2008), doi: 10.1039/b717759c
 Zhou J., et al., (2007), doi: 10.1080/17452750701747278
 Srigunapalan S., et al., (2012), doi: 10.1039/c1lc20844f
 Eydelnant I.A., et al., (2012), doi: 10.1039/c2lc21004e