Editing Digital microfluidics (section)

== Droplet manipulation ==

=== Droplet merging ===
As an existing droplet can be split to form discrete droplets using electrodes (see '''[[#From an existing droplet|From an existing droplet]]'''),<ref name="Pollack_2000" /><ref name="Cho_2003" /> droplets can be merged into one droplet by electrodes as well.<ref name="Accardo_2013">{{cite journal | vauthors = Accardo A, Mecarini F, Leoncini M, Brandi F, Di Cola E, Burghammer M, Riekel C, Di Fabrizio E | display-authors = 6 | title = Fast, active droplet interaction: coalescence and reactive mixing controlled by electrowetting on a superhydrophobic surface | journal = Lab on a Chip | volume = 13 | issue = 3 | pages = 332–335 | date = February 2013 | pmid = 23224020 | doi = 10.1039/c2lc41193h }}</ref><ref name="Cho_2003" /> Utilizing the same concept applied for creating new droplets through splitting an existing droplet with electrodes, an aqueous droplet resting on an uncharged electrode can move towards a charged electrode where droplets will join and merge into one droplet.<ref name="Accardo_2013" /><ref name="Cho_2003" /> However, the merged droplet might not always form a circular shape even after the merging process is over due to surface tension.<ref name="Cho_2003" /> This problem can be solved by implementing a superhydrophobic surface between the droplets and the electrodes.<ref name="Accardo_2013" /> Oil droplets can be merged in the same way as well, but oil droplets will move towards uncharged electrodes unlike aqueous droplets.<ref name="Wang_2011">{{Cite journal| vauthors = Wang W, Jones TB |date=2011-06-23|title=Microfluidic actuation of insulating liquid droplets in a parallel-plate device|journal=Journal of Physics: Conference Series|volume=301|issue=1|pages=012057|doi=10.1088/1742-6596/301/1/012057|bibcode=2011JPhCS.301a2057W|issn=1742-6596|doi-access=free}}</ref>

=== Droplet transportation ===
Discrete droplets can be transported in a highly controlled way using an array of electrodes.<ref>{{Cite book| vauthors = Phan SK, Hashi C, Kim CJ |title=The Sixteenth Annual International Conference on Micro Electro Mechanical Systems, 2003. MEMS-03 Kyoto. IEEE |chapter=Manipulation of multiple droplets on N×M grid by cross-reference EWOD driving scheme and pressure-contact packaging |year=2003|pages=694–697|publisher=IEEE|doi=10.1109/memsys.2003.1189844|isbn=0-7803-7744-3|s2cid=108612930}}</ref><ref>{{Cite journal| vauthors = Fair RB, Khlystov A, Tailor TD, Ivanov V, Evans RD, Srinivasan V, Pamula VK, Pollack MG, Griffin PB, Zhou J | display-authors = 6 |date=January 2007|title=Chemical and Biological Applications of Digital-Microfluidic Devices|journal=IEEE Design & Test of Computers|volume=24|issue=1|pages=10–24|doi=10.1109/MDT.2007.8|issn=0740-7475|hdl=10161/6987|s2cid=10122940|hdl-access=free}}</ref><ref name="Wang_2011" /> In the same way droplets move from an uncharged electrode to a charged electrode, or vice versa, droplets can be continuously transported along the electrodes by sequentially energizing the electrodes.<ref name="Banerjee_2015">{{cite journal| vauthors = Banerjee A, Noh JH, Liu Y, Rack PD, Papautsky I |date=2015-01-22|title=Programmable Electrowetting with Channels and Droplets|journal=Micromachines|volume=6|issue=2|pages=172–185|doi=10.3390/mi6020172|issn=2072-666X|doi-access=free}}</ref><ref name="Wang_2011" /><ref name="Cho_2003" /> Since droplet transportation involves an array of electrodes, multiple electrodes can be programmed to selectively apply a voltage to each electrode for a better control over transporting multiple droplets.<ref name="Banerjee_2015" />

=== Displacement by electrostatic actuation ===
Three-dimensional droplet actuation has been made possible by implementing a closed system; this system contains a μL sized droplet in immiscible fluid medium. The droplet and medium are then sandwiched between two electromagnetic plates, creating an EM field between the two plates.<ref name="Roux_2007">{{cite journal | vauthors = Roux JM, Fouillet Y, Achard JL | title = 3D droplet displacement in microfluidic systems by electrostatic actuation. | journal = Sensors and Actuators A: Physical | date = March 2007 | volume = 134 | issue = 2 | pages = 486–93 | doi = 10.1016/j.sna.2006.05.012 | bibcode = 2007SeAcA.134..486R | s2cid = 108644890 | url = https://hal.archives-ouvertes.fr/hal-00267651/file/Roux2007.pdf }}</ref><ref>{{cite journal | vauthors = Fouillet Y, Achard JL | title = Microfluidique discrète et biotechnologie. | journal = Comptes Rendus Physique | date = June 2004 | volume = 5 | issue = 5 | pages = 577–88 | doi = 10.1016/j.crhy.2004.04.004 | bibcode = 2004CRPhy...5..577F | url = https://hal.archives-ouvertes.fr/hal-00182327/file/fouillet2004.pdf }}</ref> The purpose of this method is to transfer the droplet from a lower planar surface to an upper parallel planar surface and back down via electrostatic forces.<ref name="Roux_2007" /><ref name="Kolar_2001">{{cite conference | vauthors = Kolar P, Fair RB | title = Non-contact electrostatic stamping for DNA microarray synthesis (poster) | conference = Proceedings of the SmallTalk2001 | location = San Diego, USA | date = 2001 }}</ref> The physics behind such particle actuation and perpendicular movement can be understood from early works of N. N. Lebedev and I. P. Skal’skaya.<ref name="Lebedev_1962">{{cite journal | vauthors = Lebedev NN, Skal'skaya IP | title = Force acting on a conducting sphere in the field of a parallel plate condenser | journal = Soviet Phys. Tech. Phys. | volume = 7 | date = 1962 | pages = 268–270 }}</ref> In their research, they attempted to model the Maxwell electrical charge acquired by a perfectly round conducting particle in the presence of a uniform magnetic field caused by a perfectly-conducting and infinitely-stretching surface.<ref name="Lebedev_1962" /> Their model helps to predict the Z-direction motion of the microdroplets within the device as it points to the magnitude and direction of forces acting upon a micro droplet. This can be used to help accurately predict and correct for unwanted and uncontrollable particle movement. The model explains why failing to employ dielectric coating on one of the two surfaces causes reversal of charge within the droplet upon contact with each electrode and in turn causes the droplets to uncontrollably bounce of between electrodes.

Digital microfluidics (DMF), has already been readily adapted in many biological fields.<ref>{{cite journal | vauthors = Velev OD, Prevo BG, Bhatt KH | title = On-chip manipulation of free droplets | journal = Nature | volume = 426 | issue = 6966 | pages = 515–6 | date = December 2003 | pmid = 14654830 | doi = 10.1038/426515a | bibcode = 2003Natur.426..515V | s2cid = 21293602 }}</ref><ref name="Gascoyne_2004">{{cite journal | vauthors = Gascoyne PR, Vykoukal JV, Schwartz JA, Anderson TJ, Vykoukal DM, Current KW, McConaghy C, Becker FF, Andrews C | title = Dielectrophoresis-based programmable fluidic processors | journal = Lab on a Chip | volume = 4 | issue = 4 | pages = 299–309 | date = August 2004 | pmid = 15269795 | doi = 10.1039/b404130e }}</ref><ref name="Taniguchi_2002">{{cite journal | vauthors = Taniguchi T, Torii T, Higuchi T | title = Chemical reactions in microdroplets by electrostatic manipulation of droplets in liquid media | journal = Lab on a Chip | volume = 2 | issue = 1 | pages = 19–23 | date = February 2002 | pmid = 15100855 | doi = 10.1039/b108739h }}</ref> By enabling three-dimensional movement within DMF, the technology can be used even more extensively in biological applications, as it could more accurately mimic 3-D microenvironments. A large benefit of employing this type of method is that it allows for two different environments to be accessible by the droplet, which can be taken advantage of by splitting the microfluidic tasks among the two surfaces. For example, while the lower plane can be used to move droplets, the upper plate can carry out the necessary chemical and/or biological processes.<ref name="Roux_2007" /> This advantage can be translated into practical experiment protocols in the biological community, such as coupling with DNA amplification.<ref>{{cite journal | vauthors = Coelho B, Veigas B, Fortunato E, Martins R, Águas H, Igreja R, Baptista PV | title = Digital Microfluidics for Nucleic Acid Amplification | journal = Sensors | volume = 17 | issue = 7 | pages = 1495 | date = June 2017 | pmid = 28672827 | pmc = 5539496 | doi = 10.3390/s17071495 | doi-access = free | bibcode = 2017Senso..17.1495C }}</ref><ref name="Kolar_2001" /><ref>{{cite journal | vauthors = Coelho BJ, Veigas B, Bettencourt L, Águas H, Fortunato E, Martins R, Baptista PV, Igreja R | display-authors = 6 | title = Digital Microfluidics-Powered Real-Time Monitoring of Isothermal DNA Amplification of Cancer Biomarker | journal = Biosensors | volume = 12 | issue = 4 | pages = 201 | date = March 2022 | pmid = 35448261 | pmc = 9028060 | doi = 10.3390/bios12040201 | doi-access = free }}</ref> This also allows for the chip to be smaller, and to give researchers more freedom in designing platforms for microdroplet analysis.<ref name="Roux_2007" />

=== All-terrain droplet actuation (ATDA) ===
All-terrain microfluidics is a method used to transport liquid droplets over non-traditional surface types.<ref name="Abdelgawad_2008">{{cite journal | vauthors = Abdelgawad M, Freire SL, Yang H, Wheeler AR | title = All-terrain droplet actuation | journal = Lab on a Chip | volume = 8 | issue = 5 | pages = 672–7 | date = May 2008 | pmid = 18432335 | doi = 10.1039/b801516c }}</ref> Unlike traditional microfluidics platform, which are generally restricted to planar and horizontal surfaces, ATDA enables droplet manipulation over curved, non-horizontal, and inverted surfaces.<ref name="Abdelgawad_2008" /> This is made possible by incorporating flexible thin sheets of copper and polyimide into the surface via a rapid prototyping method.<ref name="Abdelgawad_2008" /><ref>{{cite journal | vauthors = Abdelgawad M, Wheeler AR | title = Rapid prototyping in copper substrates for digital microfluidics. | journal = Advanced Materials | date = January 2007 | volume = 19 | issue = 1 | pages = 133–7 | doi =  10.1002/adma.200601818 | bibcode = 2007AdM....19..133A | s2cid = 53621073 }}</ref> This device works very well with many liquids, including aqueous buffers, solutions of proteins and DNA, and undiluted bovine serum.<ref name="Abdelgawad_2008" /> ATDA is compatible with silicone oil or pluronic additives, such as F-68, which reduce non-specific absorption and biofouling when dealing with biological fluids such as proteins, biological serums, and DNA.<ref name="Abdelgawad_2008" /><ref name="George_2015">{{cite journal | vauthors = George SM, Moon H | title = Digital microfluidic three-dimensional cell culture and chemical screening platform using alginate hydrogels | journal = Biomicrofluidics | volume = 9 | issue = 2 | pages = 024116 | date = March 2015 | pmid = 25945142 | pmc = 4401805 | doi = 10.1063/1.4918377 }}</ref> A drawback of a setup like this is accelerated droplet evaporation.<ref name="Abdelgawad_2008" /> ATDA is a form of open digital microfluidics, and as such the device needs to be encapsulated in a humidified environment in order to minimize droplet evaporation.<ref name="Barbulovic-Nad_2008">{{cite journal | vauthors = Barbulovic-Nad I, Yang H, Park PS, Wheeler AR | title = Digital microfluidics for cell-based assays | journal = Lab on a Chip | volume = 8 | issue = 4 | pages = 519–26 | date = April 2008 | pmid = 18369505 | doi = 10.1039/b717759c }}</ref>