Editing Microfluidics (section)

==Various kinds of microfluidic flows==
Microfluidic flows need only be constrained by geometrical length scale – the modalities and methods used to achieve such a geometrical constraint are highly dependent on the targeted application.<ref>{{Cite journal| vauthors = Thomas DJ, McCall C, Tehrani Z, Claypole TC |date=June 2017 |title=Three-Dimensional–Printed Laboratory-on-a-Chip With Microelectronics and Silicon Integration |journal=Point of Care |volume=16 |issue=2 |pages=97–101 |doi=10.1097/POC.0000000000000132 |s2cid=58306257 |url=https://cronfa.swan.ac.uk/Record/cronfa34529 }}</ref> Traditionally, microfluidic flows have been generated inside closed channels with the channel cross section being in the order of 10 μm x 10 μm. Each of these methods has its own associated techniques to maintain robust fluid flow which have matured over several years.{{citation needed|date=June 2023}}

=== Open microfluidics ===
The behavior of fluids and their control in open microchannels came into focus around 2005<ref name="Melinvan der Wijngaart2005">{{cite journal | vauthors = Melin J, van der Wijngaart W, Stemme G | title = Behaviour and design considerations for continuous flow closed-open-closed liquid microchannels | journal = Lab on a Chip | volume = 5 | issue = 6 | pages = 682–686 | date = June 2005 | pmid = 15915262 | doi = 10.1039/b501781e | url = http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-14775 }}</ref> and applied in air-to-liquid sample collection<ref name="FriskRönnholm2006">{{cite journal | vauthors = Frisk T, Rönnholm D, van der Wijngaart W, Stemme G | title = A micromachined interface for airborne sample-to-liquid transfer and its application in a biosensor system | journal = Lab on a Chip | volume = 6 | issue = 12 | pages = 1504–1509 | date = December 2006 | pmid = 17203153 | doi = 10.1039/B612526N | url = http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-14188 }}</ref><ref name="FriskSandström2008">{{cite journal | vauthors = Frisk T, Sandström N, Eng L, van der Wijngaart W, Månsson P, Stemme G | title = An integrated QCM-based narcotics sensing microsystem | journal = Lab on a Chip | volume = 8 | issue = 10 | pages = 1648–1657 | date = October 2008 | pmid = 18813386 | doi = 10.1039/b800487k | url = http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-14189 }}</ref> and chromatography.<ref name="JacksénFrisk2007">{{cite journal | vauthors = Jacksén J, Frisk T, Redeby T, Parmar V, van der Wijngaart W, Stemme G, Emmer A | title = Off-line integration of CE and MALDI-MS using a closed-open-closed microchannel system | journal = Electrophoresis | volume = 28 | issue = 14 | pages = 2458–2465 | date = July 2007 | pmid = 17577881 | doi = 10.1002/elps.200600735 | s2cid = 16337938 | doi-access = free }}</ref> In [[open microfluidics]], at least one boundary of the system is removed, exposing the fluid to air or another interface (i.e. liquid).<ref name=":1">{{cite book| vauthors = Berthier J, Brakke KA, Berthier E |date=2016-08-01|title=Open Microfluidics|doi=10.1002/9781118720936|isbn=9781118720936}}</ref><ref>{{cite journal | vauthors = Pfohl T, Mugele F, Seemann R, Herminghaus S | title = Trends in microfluidics with complex fluids | journal = ChemPhysChem | volume = 4 | issue = 12 | pages = 1291–1298 | date = December 2003 | pmid = 14714376 | doi = 10.1002/cphc.200300847 | url = https://ris.utwente.nl/ws/files/6488126/trends_in_microfluidics.pdf }}</ref><ref name=":2">{{cite journal | vauthors = Kaigala GV, Lovchik RD, Delamarche E | title = Microfluidics in the "open space" for performing localized chemistry on biological interfaces | journal = Angewandte Chemie | volume = 51 | issue = 45 | pages = 11224–11240 | date = November 2012 | pmid = 23111955 | doi = 10.1002/anie.201201798 }}</ref> Advantages of open microfluidics include accessibility to the flowing liquid for intervention, larger liquid-gas surface area, and minimized bubble formation.<ref>{{cite journal |last1=Lade |first1=R. K. |last2=Jochem |first2=K. S. |last3=Macosko |first3=C. W. |last4=Francis |first4=L. F. |date=2018 |title=Capillary Coatings: Flow and Drying Dynamics in Open Microchannels |url=https://doi.org/10.1021/acs.langmuir.8b00811 |journal=Langmuir |volume=34 |issue=26 |pages=7624–7639 | pmid=29787270 | doi=10.1021/acs.langmuir.8b00811}}</ref><ref name=":1" /><ref name=":2" /><ref>{{cite journal | vauthors = Li C, Boban M, Tuteja A | title = Open-channel, water-in-oil emulsification in paper-based microfluidic devices | journal = Lab on a Chip | volume = 17 | issue = 8 | pages = 1436–1441 | date = April 2017 | pmid = 28322402 | doi = 10.1039/c7lc00114b | s2cid = 5046916 }}</ref>  Another advantage of open microfluidics is the ability to integrate open systems with surface-tension driven fluid flow, which eliminates the need for external pumping methods such as peristaltic or syringe pumps.<ref name=":4">{{cite journal | vauthors = Casavant BP, Berthier E, Theberge AB, Berthier J, Montanez-Sauri SI, Bischel LL, Brakke K, Hedman CJ, Bushman W, Keller NP, Beebe DJ | display-authors = 6 | title = Suspended microfluidics | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 25 | pages = 10111–10116 | date = June 2013 | pmid = 23729815 | pmc = 3690848 | doi = 10.1073/pnas.1302566110 | doi-access = free | bibcode = 2013PNAS..11010111C }}</ref> Open microfluidic devices are also easy and inexpensive to fabricate by milling, thermoforming, and hot embossing.<ref>{{cite journal | vauthors = Guckenberger DJ, de Groot TE, Wan AM, Beebe DJ, Young EW | title = Micromilling: a method for ultra-rapid prototyping of plastic microfluidic devices | journal = Lab on a Chip | volume = 15 | issue = 11 | pages = 2364–2378 | date = June 2015 | pmid = 25906246 | pmc = 4439323 | doi = 10.1039/c5lc00234f }}</ref><ref>{{cite journal|vauthors = Truckenmüller R, Rummler Z, Schaller T, Schomburg WK|date=2002-06-13|title=Low-cost thermoforming of micro fluidic analysis chips|journal=Journal of Micromechanics and Microengineering|volume=12|issue=4|pages=375–379|doi=10.1088/0960-1317/12/4/304|issn=0960-1317|bibcode=2002JMiMi..12..375T|s2cid=250860338 }}</ref><ref>{{cite journal | vauthors = Jeon JS, Chung S, Kamm RD, Charest JL | title = Hot embossing for fabrication of a microfluidic 3D cell culture platform | journal = Biomedical Microdevices | volume = 13 | issue = 2 | pages = 325–333 | date = April 2011 | pmid = 21113663 | pmc = 3117225 | doi = 10.1007/s10544-010-9496-0 }}</ref><ref>{{cite journal | vauthors = Young EW, Berthier E, Guckenberger DJ, Sackmann E, Lamers C, Meyvantsson I, Huttenlocher A, Beebe DJ | display-authors = 6 | title = Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays | journal = Analytical Chemistry | volume = 83 | issue = 4 | pages = 1408–1417 | date = February 2011 | pmid = 21261280 | pmc = 3052265 | doi = 10.1021/ac102897h }}</ref> In addition, open microfluidics eliminates the need to glue or bond a cover for devices, which could be detrimental to capillary flows. Examples of open microfluidics include open-channel microfluidics, rail-based microfluidics, [[Paper-based microfluidics|paper-based]], and thread-based microfluidics.<ref name=":1" /><ref name=":4" /><ref>{{cite journal | vauthors = Bouaidat S, Hansen O, Bruus H, Berendsen C, Bau-Madsen NK, Thomsen P, Wolff A, Jonsmann J | display-authors = 6 | title = Surface-directed capillary system; theory, experiments and applications | journal = Lab on a Chip | volume = 5 | issue = 8 | pages = 827–836 | date = August 2005 | pmid = 16027933 | doi = 10.1039/b502207j | s2cid = 18125405 }}</ref>  Disadvantages to open systems include susceptibility to evaporation,<ref>{{cite journal | vauthors = Kachel S, Zhou Y, Scharfer P, Vrančić C, Petrich W, Schabel W | title = Evaporation from open microchannel grooves | journal = Lab on a Chip | volume = 14 | issue = 4 | pages = 771–778 | date = February 2014 | pmid = 24345870 | doi = 10.1039/c3lc50892g }}</ref> contamination,<ref>{{cite book | vauthors = Ogawa M, Higashi K, Miki N | title = 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)| chapter = Development of hydrogel microtubes for microbe culture in open environment | volume = 2015 | issue = 6 | pages = 5896–5899 | date = August 2015 | pmid =  26737633 | pmc =  | doi = 10.1109/EMBC.2015.7319733 | isbn = 978-1-4244-9271-8| s2cid = 4089852}}</ref> and limited flow rate.<ref name=":2" />

===Continuous-flow microfluidics===

Continuous flow microfluidics rely on the control of a steady state [[steady flow|liquid flow]] through narrow channels or porous media predominantly by accelerating or hindering fluid flow in capillary elements.<ref name="Morin 8393–8400"/> In paper based microfluidics, capillary elements can be achieved through the simple variation of section geometry. In general, the actuation of [[steady flow|liquid flow]] is implemented either by external [[pressure]] sources, external mechanical [[pump]]s, integrated mechanical [[micropump]]s, or by combinations of capillary forces and [[Electrohydrodynamics|electrokinetic]] mechanisms.<ref name=Chang>{{cite book|vauthors = Chang HC, Yeo L|title=Electrokinetically Driven Microfluidics and Nanofluidics|year=2009|publisher =[[Cambridge University Press]] }}</ref><ref>{{cite web|url=http://www.cytonix.com/fluid%20transistor.html|title=fluid transistor|archive-url=https://web.archive.org/web/20110708215908/http://www.cytonix.com/fluid%20transistor.html|archive-date=July 8, 2011}}</ref>  Continuous-flow microfluidic operation is the mainstream approach because it is easy to implement and less sensitive to protein fouling problems. Continuous-flow devices are adequate for many well-defined and simple biochemical applications, and for certain tasks such as chemical separation, but they are less suitable for tasks requiring a high degree of flexibility or fluid manipulations. These closed-channel systems are inherently difficult to integrate and scale because the parameters that govern flow field vary along the flow path making the fluid flow at any one location dependent on the properties of the entire system. Permanently etched microstructures also lead to limited reconfigurability and poor fault tolerance capability. 
[[File:Mikrofluidik_sensor.jpg|thumb|Micro fluid sensor]]
Process monitoring capabilities in continuous-flow systems can be achieved with highly sensitive microfluidic flow sensors based on [[Microelectromechanical systems|MEMS]] technology, which offers resolutions down to the nanoliter range.<ref>{{cite book |last1=Wu |first1=S. |title=Proceedings IEEE Thirteenth Annual International Conference on Micro Electro Mechanical Systems (Cat. No.00CH36308) |chapter=MEMS flow sensors for nano-fluidic applications |chapter-url=https://ieeexplore.ieee.org/document/838611 |website=IEEE Explore |date=2000 |pages=745–750 |publisher=IEEE |doi=10.1109/MEMSYS.2000.838611 |isbn=0-7803-5273-4 |url=https://resolver.caltech.edu/CaltechAUTHORS:WUSmems00 |access-date=24 January 2024}}</ref>

===Droplet-based microfluidics===

{{Main|Droplet-based microfluidics}}
[[File: Gas4psi LONDs26uLmin-1 50kfps x10lens.webm|thumb|High frame rate video showing microbubble pinch-off formation in a flow-focusing microfluidic device<ref name=DOI153>{{cite web|url=https://archive.researchdata.leeds.ac.uk/327/|doi = 10.5518/153|year = 2018| vauthors = Churchman AH |title = Data associated with 'Combined flow-focus and self-assembly routes for the formation of lipid stabilized oil-shelled microbubbles'|publisher = University of Leeds}}</ref>]]

Droplet-based microfluidics is differs from continuous microfluidics; droplet-based microfluidics manipulates discrete volumes of fluids in immiscible phases with low Reynolds number and laminar flow regimes. Interest in droplet-based microfluidics systems has been growing substantially in past decades. Microdroplets allow for handling miniature volumes (μL to fL) of fluids conveniently, provide better mixing, encapsulation, sorting, and sensing, and suit high throughput experiments.<ref name="pubs.rsc.org">{{cite journal | vauthors = Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S, Thiele J, Figdor CG, Huck WT | display-authors = 6 | title = Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics | journal = Lab on a Chip | volume = 13 | issue = 24 | pages = 4740–4744 | date = December 2013 | pmid = 24185478 | doi = 10.1039/C3LC50945A | s2cid = 46363431 }}</ref> Exploiting the benefits of droplet-based microfluidics efficiently requires a deep understanding of droplet generation<ref name="droplet microfluidics" /> to perform various logical operations<ref name=":0">{{cite journal | vauthors = Teh SY, Lin R, Hung LH, Lee AP | title = Droplet microfluidics | journal = Lab on a Chip | volume = 8 | issue = 2 | pages = 198–220 | date = February 2008 | pmid = 18231657 | doi = 10.1039/B715524G | s2cid = 18158748 }}</ref><ref>{{cite journal | vauthors = Prakash M, Gershenfeld N | title = Microfluidic bubble logic | journal = Science | volume = 315 | issue = 5813 | pages = 832–835 | date = February 2007 | pmid = 17289994 | doi = 10.1126/science.1136907 | s2cid = 5882836 | citeseerx = 10.1.1.673.2864 | bibcode = 2007Sci...315..832P }}</ref> such as droplet manipulation,<ref>{{cite journal | vauthors = Tenje M, Fornell A, Ohlin M, Nilsson J | title = Particle Manipulation Methods in Droplet Microfluidics | journal = Analytical Chemistry | volume = 90 | issue = 3 | pages = 1434–1443 | date = February 2018 | pmid = 29188994 | doi = 10.1021/acs.analchem.7b01333 | s2cid = 46777312 | doi-access = free }}</ref> droplet sorting,<ref>{{cite journal | vauthors = Xi HD, Zheng H, Guo W, Gañán-Calvo AM, Ai Y, Tsao CW, Zhou J, Li W, Huang Y, Nguyen NT, Tan SH | display-authors = 6 | title = Active droplet sorting in microfluidics: a review | journal = Lab on a Chip | volume = 17 | issue = 5 | pages = 751–771 | date = February 2017 | pmid = 28197601 | doi = 10.1039/C6LC01435F }}</ref> droplet merging,<ref>{{cite journal | vauthors = Niu X, Gulati S, Edel JB, deMello AJ | title = Pillar-induced droplet merging in microfluidic circuits | journal = Lab on a Chip | volume = 8 | issue = 11 | pages = 1837–1841 | date = November 2008 | pmid = 18941682 | doi = 10.1039/b813325e }}</ref> and droplet breakup.<ref>{{cite journal | vauthors = Samie M, Salari A, Shafii MB | title = Breakup of microdroplets in asymmetric T junctions | journal = Physical Review E | volume = 87 | issue = 5 | pages = 053003 | date = May 2013 | pmid = 23767616 | doi = 10.1103/PhysRevE.87.053003 | bibcode = 2013PhRvE..87e3003S }}</ref>

===Digital microfluidics===

{{Main|Digital microfluidics}}
Alternatives to the above closed-channel continuous-flow systems include novel open structures, where discrete, independently controllable droplets
are manipulated on a substrate using [[electrowetting]]. Following the analogy of digital microelectronics, this approach is referred to as [[digital microfluidics]]. Le Pesant et al. pioneered the use of electrocapillary forces to move droplets on a digital track.<ref>Le Pesant et al., Electrodes for a device operating by electrically controlled fluid displacement, [https://worldwide.espacenet.com/patent/search/family/009290366/publication/US4569575A?q=pn%3DUS4569575 U.S. Pat. No. 4,569,575], Feb. 11, 1986.</ref> The "fluid transistor" pioneered by Cytonix<ref>[https://www.nsf.gov/awardsearch/piSearch.do;jsessionid=D05E82394F781CBA17DB0C5AC8E3C0B8?SearchType=piSearch&page=1&QueryText=&PIFirstName=james&PILastName=brown&PIInstitution=cytonix&PIState=MD&PIZip=&PICountry=US&RestrictExpired=on&Search=Search#results NSF Award Search: Advanced Search Results<!-- Bot generated title -->]</ref> also played a role. The technology was subsequently commercialised by Duke University. By using discrete unit-volume droplets,<ref name="droplet microfluidics">{{cite journal|vauthors = Chokkalingam V, Herminghaus S, Seemann R|year = 2008|title = Self-synchronizing Pairwise Production of Monodisperse Droplets by Microfluidic Step Emulsification|url = http://apl.aip.org/applab/v93/i25/p254101_s1|journal = Applied Physics Letters|volume = 93|issue =  25|page = 254101|doi = 10.1063/1.3050461|bibcode = 2008ApPhL..93y4101C|url-status = dead|archive-url = https://archive.today/20130113004540/http://apl.aip.org/applab/v93/i25/p254101_s1|archive-date = 2013-01-13 }}</ref>  a microfluidic function can be reduced to a set of repeated basic operations, i.e., moving one unit of fluid over one unit of distance. This "digitisation" method facilitates the use of a hierarchical and cell-based approach for microfluidic biochip design. Therefore, digital microfluidics offers a flexible and scalable system architecture as well as high [[fault-tolerance]] capability. Moreover, because each droplet can be controlled independently, these systems also have dynamic reconfigurability, whereby groups of unit cells in a microfluidic array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. Although droplets are manipulated in confined microfluidic channels, since the control on droplets is not independent, it should not be confused as "digital microfluidics". One common actuation method for digital microfluidics is [[electrowetting]]-on-dielectric ([[EWOD]]).<ref>{{cite journal| vauthors = Lee J, Kim CJ |s2cid=25996316|date=June 2000|title=Surface-tension-driven microactuation based on continuous electrowetting|journal=Journal of Microelectromechanical Systems|volume=9|issue=2|pages=171–180|doi=10.1109/84.846697|issn=1057-7157}}</ref> Many lab-on-a-chip applications have been demonstrated within the digital microfluidics paradigm using electrowetting. 

=== Paper-based microfluidics ===
{{Main|Paper-based microfluidics}}
Paper-based microfluidic devices are proposed to provide portable, cheap, and user-friendly medical diagnostic systems.<ref name=":03">{{cite book|title=Open Microfluidics| vauthors = Berthier J, Brakke KA, Berthier E |date=2016|publisher=John Wiley & Sons, Inc.|isbn=9781118720936|pages=229–256|language=en|doi=10.1002/9781118720936.ch7}}</ref> 
Paper based microfluidics rely on the phenomenon of capillary penetration in porous media.<ref name=porous>{{cite journal | vauthors = Liu M, Suo S, Wu J, Gan Y, Ah Hanaor D, Chen CQ | title = Tailoring porous media for controllable capillary flow | journal = Journal of Colloid and Interface Science | volume = 539 | pages = 379–387 | date = March 2019 | pmid = 30594833 | doi = 10.1016/j.jcis.2018.12.068 | arxiv = 2106.03526 | s2cid = 58553777 | bibcode = 2019JCIS..539..379L }}</ref> To tune fluid penetration in porous substrates such as paper in two and three dimensions, the pore structure, wettability and geometry of the microfluidic devices can be controlled while the viscosity and evaporation rate of the liquid play a further significant role. Many such devices feature hydrophobic barriers on hydrophilic paper that passively transport aqueous solutions to outlets where biological reactions take place.<ref name=":3">{{cite book|url=https://books.google.com/books?id=5YQlDwAAQBAJ&q=Microfabrication+Techniques+for+Microfluidic+Devices+Silverio&pg=PA24|title=Complex Fluid-Flows in Microfluidics| vauthors = Galindo-Rosales FJ |date=2017-05-26|publisher=Springer|isbn=9783319595931|language=en}}</ref> Paper-based microfluidics are considered as portable point-of-care biosensors used in a remote setting where advanced medical diagnostic tools are not accessible.<ref>{{cite journal | vauthors = Loo J, Ho A, Turner A, Mak WC | title = Integrated Printed Microfluidic Biosensors | journal = Trends in Biotechnology | volume = 37 | issue = 10 | pages = 1104–1120 | date = 2019 | pmid = 30992149 | doi = 10.1016/j.tibtech.2019.03.009 | hdl = 1826/15985 | s2cid = 119536401 | hdl-access = free }}</ref> Current applications include portable glucose detection<ref name=":52">{{cite journal | vauthors = Martinez AW, Phillips ST, Butte MJ, Whitesides GM | title = Patterned paper as a platform for inexpensive, low-volume, portable bioassays | journal = Angewandte Chemie | volume = 46 | issue = 8 | pages = 1318–1320 | date = 2007 | pmid = 17211899 | pmc = 3804133 | doi = 10.1002/anie.200603817 }}</ref> and environmental testing,<ref name=":72">{{cite journal|url=https://www.researchgate.net/publication/271508549|title=Smartphone Detection of Escherichia coli From Field Water Samples on Paper Microfluidics |journal=IEEE Sensors Journal| vauthors = Park TS, Yoon JY |s2cid=34581378 |date=2015-03-01 |volume=15 |issue=3 |pages=1902 |bibcode=2015ISenJ..15.1902P |doi=10.1109/JSEN.2014.2367039}}</ref> with hopes of reaching areas that lack advanced medical diagnostic tools.

=== Particle detection microfluidics ===
One potential application area involves particle detection in fluids. Particle detection of small fluid-borne particles down to about 1 μm in diameter is typically achieved using a [[Coulter counter]], in which electrical signals are generated when a weakly-conducting fluid such as in [[saline water]] is passed through a small (~100 μm diameter) pore, so that an electrical signal is generated that is directly proportional to the ratio of the particle volume to the pore volume. The physics behind this is relatively simple, described in a classic paper by DeBlois and Bean,<ref>{{cite journal| vauthors = DeBlois RW, Bean CP |title=Counting and sizing of submicron particles by the resistive pulse technique|journal=Rev. Sci. Instrum.|date=1970|volume=41|issue=7|pages=909–916|doi=10.1063/1.1684724|bibcode=1970RScI...41..909D }}</ref> and the implementation first described in Coulter's original patent.<ref>{{cite patent|country=US|number=2656508|status=|title=Means for counting particles suspended in a fluid|pubdate=Oct. 20, 1953|inventor=Wallace H. Coulter}}</ref> This is the method used to e.g. size and count erythrocytes ([[red blood cells]]) as well as leukocytes ([[white blood cell]]s) for standard blood analysis. The generic term for this method is [[resistive pulse sensing]] (RPS); Coulter counting is a trademark term. However, the RPS method does not work well for particles below 1 μm diameter, as the [[signal-to-noise ratio]] falls below the reliably detectable limit, set mostly by the size of the pore in which the analyte passes and the input noise of the first-stage [[amplifier]].{{citation needed|date=June 2023}}

The limit on the pore size in traditional RPS Coulter counters is set by the method used to make the pores, which while a trade secret, most likely{{according to whom|date=October 2020}} uses traditional mechanical methods. This is where microfluidics can have an impact: The [[lithography]]-based production of microfluidic devices, or more likely the production of reusable molds for making microfluidic devices using a [[Molding (process)|molding]] process, is limited to sizes much smaller than traditional [[machining]]. Critical dimensions down to 1 μm are easily fabricated, and with a bit more effort and expense, feature sizes below 100&nbsp;nm can be patterned reliably as well. This enables the inexpensive production of pores integrated in a microfluidic circuit where the pore diameters can reach sizes of order 100&nbsp;nm, with a concomitant reduction in the minimum particle diameters by several orders of magnitude.

As a result, there has been some university-based development of microfluidic particle counting and sizing<ref>{{cite journal | vauthors = Lewpiriyawong N, Yang C | title = AC-dielectrophoretic characterization and separation of submicron and micron particles using sidewall AgPDMS electrodes | journal = Biomicrofluidics | volume = 6 | issue = 1 | pages = 12807–128079 | date = March 2012 | pmid = 22662074 | pmc = 3365326 | doi = 10.1063/1.3682049 }}</ref><ref>{{cite journal | vauthors = Gnyawali V, Strohm EM, Wang JZ, Tsai SS, Kolios MC | title = Simultaneous acoustic and photoacoustic microfluidic flow cytometry for label-free analysis | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 1585 | date = February 2019 | pmid = 30733497 | pmc = 6367457 | doi = 10.1038/s41598-018-37771-5 | bibcode = 2019NatSR...9.1585G }}</ref><ref>{{cite journal | vauthors = Weiss AC, Krüger K, Besford QA, Schlenk M, Kempe K, Förster S, Caruso F | title = In Situ Characterization of Protein Corona Formation on Silica Microparticles Using Confocal Laser Scanning Microscopy Combined with Microfluidics | journal = ACS Applied Materials & Interfaces | volume = 11 | issue = 2 | pages = 2459–2469 | date = January 2019 | pmid = 30600987 | doi = 10.1021/acsami.8b14307 | hdl = 11343/219876 | s2cid = 58555221 | hdl-access = free }}</ref> with the accompanying commercialization of this technology. This method has been termed microfluidic [[resistive pulse sensing]] (MRPS).

=== Microfluidic-assisted magnetophoresis ===
One application for microfluidic devices is the separation and sorting of different fluids or cell types. Microfluidic devices have been integrated with [[wiktionary:magnetophoresis|magnetophoresis]]: the migration of particles by a [[magnetic field]].<ref>{{cite journal | vauthors = Munaz A, Shiddiky MJ, Nguyen NT | title = Recent advances and current challenges in magnetophoresis based micro magnetofluidics | journal = Biomicrofluidics | volume = 12 | issue = 3 | pages = 031501 | date = May 2018 | pmid = 29983837 | pmc = 6013300 | doi = 10.1063/1.5035388 }}</ref> This can be accomplished by sending a fluid containing at least one magnetic component through a microfluidic channel that has a [[magnet]] positioned along the length of the channel. This creates a magnetic field inside the microfluidic channel which draws [[Magnetism|magnetically]] active substances towards it, effectively separating the magnetic and non-magnetic components of the fluid. This technique can be readily utilized in [[Industry (manufacturing)|industrial]] settings where the fluid at hand already contains magnetically active material. For example, a handful of [[Metal|metallic impurities]] can find their way into certain consumable liquids, namely [[milk]] and other [[dairy]] products.<ref name="sciencedirect.com">{{cite journal| vauthors = Dibaji S, Rezai P |date=2020-06-01|title=Triplex Inertia-Magneto-Elastic (TIME) sorting of microparticles in non-Newtonian fluids |journal=Journal of Magnetism and Magnetic Materials|language=en|volume=503|pages=166620|doi=10.1016/j.jmmm.2020.166620|bibcode=2020JMMM..50366620D|s2cid=213233645|issn=0304-8853}}</ref> Conveniently, in the case of milk, many of these metal contaminants exhibit [[paramagnetism]]. Therefore, before packaging, milk can be flowed through channels with magnetic gradients as a means of purifying out the metal contaminants.

[[Cell (biology)|cell]] separations are of interest in microfluidics. This is accomplished. First, a paramagnetic substance (usually micro/[[nanoparticle]]s or a [[Ferrofluid|paramagnetic fluid]])<ref>{{cite journal | vauthors = Alnaimat F, Dagher S, Mathew B, Hilal-Alnqbi A, Khashan S | title = Microfluidics Based Magnetophoresis: A Review | journal = Chemical Record | volume = 18 | issue = 11 | pages = 1596–1612 | date = November 2018 | pmid = 29888856 | doi = 10.1002/tcr.201800018 | s2cid = 47016122 }}</ref> needs to be [[Functional group|functionalized]] to target the cell type of interest. This can be accomplished by identifying a [[Membrane protein|transmembranal protein]] unique to the cell type of interest and subsequently functionalizing magnetic particles with the complementary [[antigen]] or [[antibody]].<ref name="sciencedirect.com"/><ref>{{cite journal | vauthors = Unni M, Zhang J, George TJ, Segal MS, Fan ZH, Rinaldi C | title = Engineering magnetic nanoparticles and their integration with microfluidics for cell isolation | journal = Journal of Colloid and Interface Science | volume = 564 | pages = 204–215 | date = March 2020 | pmid = 31911225 | pmc = 7023483 | doi = 10.1016/j.jcis.2019.12.092 | bibcode = 2020JCIS..564..204U }}</ref><ref>{{cite journal | vauthors = Xia N, Hunt TP, Mayers BT, Alsberg E, Whitesides GM, Westervelt RM, Ingber DE | title = Combined microfluidic-micromagnetic separation of living cells in continuous flow | journal = Biomedical Microdevices | volume = 8 | issue = 4 | pages = 299–308 | date = December 2006 | pmid = 17003962 | doi = 10.1007/s10544-006-0033-0 | s2cid = 14534776 }}</ref><ref name="Magnetism and microfluidics">{{cite journal | vauthors = Pamme N | title = Magnetism and microfluidics | journal = Lab on a Chip | volume = 6 | issue = 1 | pages = 24–38 | date = January 2006 | pmid = 16372066 | doi = 10.1039/B513005K }}</ref><ref>{{cite journal | vauthors = Song K, Li G, Zu X, Du Z, Liu L, Hu Z | title = The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review | journal = Micromachines | volume = 11 | issue = 3 | pages = 297 | date = March 2020 | pmid = 32168977 | pmc = 7143183 | doi = 10.3390/mi11030297 | doi-access = free }}</ref> Once the magnetic particles are functionalized, they are dispersed in a cell mixture where they bind to only the cells of interest. The resulting cell/particle mixture can then be flowed through a microfluidic device with a magnetic field to separate the targeted cells from the rest.

Conversely, microfluidic-assisted magnetophoresis may be used to facilitate efficient mixing within microdroplets or plugs. To accomplish this, microdroplets are injected with paramagnetic nanoparticles and are flowed through a straight channel which passes through rapidly alternating magnetic fields. This causes the magnetic particles to be quickly pushed from side to side within the droplet and results in the mixing of the microdroplet contents.<ref name="Magnetism and microfluidics"/> This eliminates the need for tedious engineering considerations that are necessary for traditional, channel-based droplet mixing. Other research has also shown that the label-free separation of cells may be possible by suspending cells in a paramagnetic fluid and taking advantage of the magneto-Archimedes effect.<ref>{{cite journal| vauthors = Gao QH, Zhang WM, Zou HX, Li WB, Yan H, Peng ZK, Meng G |date=2019|title=Label-free manipulation via the magneto-Archimedes effect: fundamentals, methodology and applications|url=http://xlink.rsc.org/?DOI=C8MH01616J|journal=Materials Horizons |volume=6 |issue=7 |pages=1359–1379 |doi=10.1039/C8MH01616J|s2cid=133309954|issn=2051-6347}}</ref><ref>{{cite journal| vauthors = Akiyama Y, Morishima K |date=2011-04-18|title=Label-free cell aggregate formation based on the magneto-Archimedes effect|journal=Applied Physics Letters|volume=98|issue=16|pages=163702|doi=10.1063/1.3581883|bibcode=2011ApPhL..98p3702A|issn=0003-6951}}</ref> While this does eliminate the complexity of particle functionalization, more research is needed to fully understand the magneto-Archimedes phenomenon and how it can be used to this end. This is not an exhaustive list of the various applications of microfluidic-assisted magnetophoresis; the above examples merely highlight the versatility of this [[Separation process|separation technique]] in both current and future applications.