Editing Digital microfluidics (section)

=== Separation and extraction ===
Digital [[microfluidics]] can be used for separation and extraction of target analytes. These methods include the use of magnetic particles,<ref name = "Wang_2007">{{cite journal| vauthors = Wang Y, Zhao Y, Cho SK |title=Efficient in-droplet separation of magnetic particles for digital microfluidics|journal=Journal of Micromechanics and Microengineering|date=1 October 2007|volume=17|issue=10|pages=2148–2156|doi=10.1088/0960-1317/17/10/029|bibcode=2007JMiMi..17.2148W|s2cid=135789543 }}</ref><ref name = "Vergauwe_2014">{{cite journal| vauthors = Vergauwe N, Vermeir S, Wacker JB, Ceyssens F, Cornaglia M, Puers R, Gijs MA, Lammertyn J, Witters D | display-authors = 6 |title=A highly efficient extraction protocol for magnetic particles on a digital microfluidic chip|journal=Sensors and Actuators B: Chemical|date=June 2014|volume=196|pages=282–291|doi=10.1016/j.snb.2014.01.076| bibcode = 2014SeAcB.196..282V }}</ref><ref name = "Seale_2016">{{cite journal | vauthors = Seale B, Lam C, Rackus DG, Chamberlain MD, Liu C, Wheeler AR | title = Digital Microfluidics for Immunoprecipitation | journal = Analytical Chemistry | volume = 88 | issue = 20 | pages = 10223–10230 | date = October 2016 | pmid = 27700039 | doi = 10.1021/acs.analchem.6b02915 }}</ref><ref name = "Shah_2009">{{cite journal| vauthors = Shah GJ, Kim CJ |title=Meniscus-Assisted High-Efficiency Magnetic Collection and Separation for EWOD Droplet Microfluidics|journal=Journal of Microelectromechanical Systems|date=April 2009|volume=18|issue=2|pages=363–375|doi=10.1109/JMEMS.2009.2013394|s2cid=24845666}}</ref><ref name = "Jebrail_2014">{{cite journal | vauthors = Jebrail MJ, Sinha A, Vellucci S, Renzi RF, Ambriz C, Gondhalekar C, Schoeniger JS, Patel KD, Branda SS | display-authors = 6 | title = World-to-digital-microfluidic interface enabling extraction and purification of RNA from human whole blood | journal = Analytical Chemistry | volume = 86 | issue = 8 | pages = 3856–3862 | date = April 2014 | pmid = 24479881 | doi = 10.1021/ac404085p }}</ref><ref name = "Hung_2015">{{cite journal| vauthors = Hung PY, Jiang PS, Lee EF, Fan SK, Lu YW |title=Genomic DNA extraction from whole blood using a digital microfluidic (DMF) platform with magnetic beads|journal=Microsystem Technologies|date= April 2015|volume=23|issue=2|pages=313–320|doi=10.1007/s00542-015-2512-9|s2cid=137531469}}</ref><ref name = "Choi_2013">{{cite journal | vauthors = Choi K, Ng AH, Fobel R, Chang-Yen DA, Yarnell LE, Pearson EL, Oleksak CM, Fischer AT, Luoma RP, Robinson JM, Audet J, Wheeler AR | display-authors = 6 | title = Automated digital microfluidic platform for magnetic-particle-based immunoassays with optimization by design of experiments | journal = Analytical Chemistry | volume = 85 | issue = 20 | pages = 9638–9646 | date = October 2013 | pmid = 23978190 | doi = 10.1021/ac401847x }}</ref><ref name = "Choi_2016">{{cite journal | vauthors = Choi K, Boyacı E, Kim J, Seale B, Barrera-Arbelaez L, Pawliszyn J, Wheeler AR | title = A digital microfluidic interface between solid-phase microextraction and liquid chromatography-mass spectrometry | journal = Journal of Chromatography A | volume = 1444 | pages = 1–7 | date = April 2016 | pmid = 27048987 | doi = 10.1016/j.chroma.2016.03.029 }}</ref> [[liquid-liquid extraction]],<ref name = "Wijethunga_2011">{{cite journal | vauthors = Wijethunga PA, Nanayakkara YS, Kunchala P, Armstrong DW, Moon H | title = On-chip drop-to-drop liquid microextraction coupled with real-time concentration monitoring technique | journal = Analytical Chemistry | volume = 83 | issue = 5 | pages = 1658–1664 | date = March 2011 | pmid = 21294515 | doi = 10.1021/ac102716s }}</ref> [[optical tweezers]],<ref name = "Shah_2009b">{{cite journal | vauthors = Shah GJ, Ohta AT, Chiou EP, Wu MC, Kim CJ | title = EWOD-driven droplet microfluidic device integrated with optoelectronic tweezers as an automated platform for cellular isolation and analysis | journal = Lab on a Chip | volume = 9 | issue = 12 | pages = 1732–1739 | date = June 2009 | pmid = 19495457 | doi = 10.1039/b821508a }}</ref> and [[Fluid dynamics|hydrodynamic effects]].<ref name = "Nejad_2015">{{cite journal| vauthors = Nejad HR, Samiei E, Ahmadi A, Hoorfar M |title=Gravity-driven hydrodynamic particle separation in digital microfluidic systems |journal=RSC Adv. |date=2015 |volume=5 |issue=45 |pages=35966–35975 |doi=10.1039/C5RA02068A|bibcode=2015RSCAd...535966N }}</ref>

==== Magnetic particles ====
For magnetic particle separations a droplet of solution containing the analyte of interest is placed on a digital microfluidics [[electrode array]] and moved by the changes in the charges of the electrodes. The droplet is moved to an electrode with a magnet on one side of the array with magnetic particles functionalized to bind to the analyte. Then it is moved over the electrode, the magnetic field is removed and the particles are suspended in the droplet. The droplet is swirled on the electrode array to ensure mixing. The magnet is reintroduced and the particles are immobilized and the droplet is moved away. This process is repeated with wash and elution buffers to extract the analyte.<ref name="Wang_2007" /><ref name="Vergauwe_2014" /><ref name="Seale_2016" /><ref name="Shah_2009" /><ref name="Jebrail_2014" /><ref name="Hung_2015" /><ref name="Choi_2013" /><ref name="Choi_2016" />

Magnetic particles coated with antihuman [[serum albumin]] antibodies have been used to isolate human serum albumin, as proof of concept work for immunoprecipitation using digital microfluidics.<sup>5</sup> DNA extraction from a whole blood sample has also been performed with digital microfluidics.<sup>3</sup> The procedure follows the general methodology  as the magnetic particles, but includes pre-treatment on the digital microfluidic platform to [[Lysis|lyse]] the cells prior to DNA extraction.<ref name="Seale_2016" />

==== Liquid-liquid extraction ====
[[Liquid-liquid extraction]]s can be carried out on digital microfluidic device by taking advantage of immiscible liquids.<sup>9</sup> Two droplets, one containing the analyte in aqueous phase, and the other an immiscible ionic liquid are present on the electrode array. The two droplets are mixed and the ionic liquid extracts the analyte, and the droplets are easily separable.<ref name="Wijethunga_2011" />

==== Optical tweezers ====
[[Optical tweezers]] have also been used to separate cells in droplets. Two droplets are mixed on an electrode array, one containing the cells, and the other with nutrients or drugs. The droplets are mixed and then optical tweezers are used to move the cells to one side of the larger droplet before it is split.<ref>{{cite journal | vauthors = Neuman KC, Block SM | title = Optical trapping | journal = The Review of Scientific Instruments | volume = 75 | issue = 9 | pages = 2787–809 | date = September 2004 | pmid = 16878180 | pmc = 1523313 | doi = 10.1063/1.1785844 | bibcode = 2004RScI...75.2787N }}</ref><ref name="Shah_2009b" /> For a more detailed explanation on the underlying principles, see [[Optical tweezers]].

==== Hydrodynamic separation ====
Particles have been applied for use outside of magnetic separation, with hydrodynamic forces to separate particles from the bulk of a droplet.<ref name="Nejad_2015" /> This is performed on electrode arrays with a central electrode and ‘slices’ of electrodes surrounding it. Droplets are added onto the array and swirled in a circular pattern, and the hydrodynamic forces from the swirling cause the particles to aggregate onto the central electrode.<ref name="Nejad_2015" />