Array ( [0] => {{short description|Interdisciplinary science}} [1] => [[File:Microfluidic Device (6842746147).jpg|alt=Microfluidic device|thumb|NIST researchers have combined a glass slide, plastic sheets and double-sided tape to create an inexpensive and simple-to-build microfluidic device for exposing an array of cells to different concentrations of a chemical.]] [2] => '''Microfluidics''' refers to a system that manipulates a small amount of [[fluids]] (10−9 to 10−18 liters) using small channels with sizes ten to hundreds micrometres. It is a multidisciplinary field that involves molecular analysis, [[molecular biology]], and [[microelectronics]].{{Cite journal |last=Whitesides |first=George M. |date=July 2006 |title=The origins and the future of microfluidics |url=http://www.nature.com/articles/nature05058 |journal=Nature |language=en |volume=442 |issue=7101 |pages=368–373 |doi=10.1038/nature05058 |pmid=16871203 |bibcode=2006Natur.442..368W |s2cid=205210989 |issn=0028-0836}} It has practical applications in the design of systems that process low volumes of fluids to achieve [[multiplexing]], automation, and [[high-throughput screening]]. Microfluidics emerged in the beginning of the 1980s and is used in the development of [[inkjet]] printheads, [[DNA chip]]s, [[lab-on-a-chip]] technology, micro-propulsion, and micro-thermal technologies. [3] => [4] => Typically, micro means one of the following features: [5] => [6] => * Small volumes (μL, nL, pL, fL) [7] => * Small size [8] => * Low energy consumption [9] => * Microdomain effects [10] => [11] => Typically microfluidic systems transport, mix, separate, or otherwise process fluids. Various applications rely on passive fluid control using [[capillary force]]s, in the form of capillary flow modifying elements, akin to flow resistors and flow accelerators. In some applications, external actuation means are additionally used for a directed transport of the media. Examples are rotary drives applying centrifugal forces for the fluid transport on the passive chips. '''Active microfluidics''' refers to the defined manipulation of the working fluid by active (micro) components such as [[micropump]]s or [[microvalve]]s. Micropumps supply fluids in a continuous manner or are used for dosing. Microvalves determine the flow direction or the mode of movement of pumped liquids. Often, processes normally carried out in a lab are miniaturised on a single chip, which enhances efficiency and mobility, and reduces sample and reagent volumes. [12] => [13] => ==Microscale behaviour of fluids== [14] => [[File:Microfluidics.jpg|250px|thumb|right|Silicone rubber and glass microfluidic devices. Top: a photograph of the devices. Bottom: [[Phase contrast]] [[micrograph]]s of a serpentine channel ~15 [[μm]] wide.]] [15] => The behaviour of fluids at the microscale can differ from "macrofluidic" behaviour in that factors such as [[surface tension]], energy dissipation, and fluidic resistance start to dominate the system. Microfluidics studies how these behaviours change, and how they can be worked around, or exploited for new uses.{{cite journal|vauthors = Terry SC, Jerman JH, Angell JB|s2cid = 21971431|title = A gas chromatographic air analyzer fabricated on a silicon wafer.|journal = IEEE Transactions on Electron Devices|date = December 1979|volume = 26|issue = 12|pages = 1880–6|doi = 10.1109/T-ED.1979.19791|bibcode = 1979ITED...26.1880T }}{{cite book|vauthors=Kirby BJ|title=Micro- and Nanoscale Fluid Mechanics: Transport in Microfluidic Devices|url=http://www.kirbyresearch.com/textbook|year=2010|publisher=[[Cambridge University Press]]|access-date=2010-02-13|archive-date=2019-04-28|archive-url=https://web.archive.org/web/20190428234717/http://www.kirbyresearch.com/textbook/|url-status=dead }}{{cite book|vauthors = Karniadakis GM, Beskok A, Aluru N|title=Microflows and Nanoflows|year=2005|publisher =[[Springer Verlag]] }}{{cite book|vauthors = Bruus H|title=Theoretical Microfluidics|year=2007|publisher =[[Oxford University Press]] }}{{cite book|title=Principles of Microfluidics|vauthors = Shkolnikov V|year=2019|isbn=978-1790217281}} [16] => [17] => At small scales (channel size of around 100 [[nanometers]] to 500 [[micrometers]]) some interesting and sometimes unintuitive properties appear. In particular, the [[Reynolds number]] (which compares the effect of the momentum of a fluid to the effect of [[viscosity]]) can become very low. A key consequence is co-flowing fluids do not necessarily mix in the traditional sense, as flow becomes [[laminar flow|laminar]] rather than [[turbulent flow|turbulent]]; molecular transport between them must often be through [[diffusion]].{{cite book|vauthors = Tabeling P|title=Introduction to Microfluidics|url=https://archive.org/details/introductiontomi0000tabe|url-access=registration|year=2005|publisher =[[Oxford University Press]] |isbn=978-0-19-856864-3}} [18] => [19] => High specificity of chemical and physical properties (concentration, pH, temperature, shear force, etc.) can also be ensured resulting in more uniform reaction conditions and higher grade products in single and multi-step reactions.{{cite journal | vauthors = Chokkalingam V, Weidenhof B, Krämer M, Maier WF, Herminghaus S, Seemann R | title = Optimized droplet-based microfluidics scheme for sol-gel reactions | journal = Lab on a Chip | volume = 10 | issue = 13 | pages = 1700–1705 | date = July 2010 | pmid = 20405061 | doi = 10.1039/b926976b }}{{cite journal | vauthors = Shestopalov I, Tice JD, Ismagilov RF | title = Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system | journal = Lab on a Chip | volume = 4 | issue = 4 | pages = 316–321 | date = August 2004 | pmid = 15269797 | doi = 10.1039/b403378g | url = https://authors.library.caltech.edu/40869/ }} [20] => [21] => ==Various kinds of microfluidic flows== [22] => 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.{{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 }} 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}} [23] => [24] => === Open microfluidics === [25] => The behavior of fluids and their control in open microchannels was pioneered around 2005{{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 }} and applied in air-to-liquid sample collection{{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 }}{{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 }} and chromatography.{{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 }} In [[open microfluidics]], at least one boundary of the system is removed, exposing the fluid to air or another interface (i.e. liquid).{{cite book| vauthors = Berthier J, Brakke KA, Berthier E |date=2016-08-01|title=Open Microfluidics|doi=10.1002/9781118720936|isbn=9781118720936}}{{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 }}{{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 }} Advantages of open microfluidics include accessibility to the flowing liquid for intervention, larger liquid-gas surface area, and minimized bubble formation.{{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}}{{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 }} 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.{{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 }} Open microfluidic devices are also easy and inexpensive to fabricate by milling, thermoforming, and hot embossing.{{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 }}{{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 }}{{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 }}{{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 }} 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.{{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 }} Disadvantages to open systems include susceptibility to evaporation,{{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 }} contamination,{{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}} and limited flow rate. [26] => [27] => ===Continuous-flow microfluidics=== [28] => [29] => 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. 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.{{cite book|vauthors = Chang HC, Yeo L|title=Electrokinetically Driven Microfluidics and Nanofluidics|year=2009|publisher =[[Cambridge University Press]] }}{{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}} 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. Computer-aided design automation approaches for continuous-flow microfluidics have been proposed in recent years to alleviate the design effort and to solve the scalability problems.{{cite journal | vauthors = Tseng TM, Li M, Freitas DN, McAuley T, Li B, Ho TY, Araci IE, Schlichtmann U |doi = 10.1109/TCAD.2017.2760628|title = Columba 2.0: A Co-Layout Synthesis Tool for Continuous-Flow Microfluidic Biochips|year = 2018 |s2cid = 49893963 |journal = IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems|volume = 37|issue = 8|pages = 1588–1601}} [30] => [[File:Mikrofluidik_sensor.jpg|thumb|micro fluid sensor]] [31] => 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.{{cite web |last1=Wu |first1=S. |title=MEMS flow sensors for nano-fluidic applications |url=https://ieeexplore.ieee.org/document/838611 |website=IEEE Explore |publisher=IEEE |access-date=24 January 2024}} [32] => [33] => ===Droplet-based microfluidics=== [34] => [35] => {{Main|Droplet-based microfluidics}} [36] => [[File: Gas4psi LONDs26uLmin-1 50kfps x10lens.webm|thumb|High frame rate video showing microbubble pinch-off formation in a flow-focusing microfluidic device{{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}}]] [37] => [38] => Droplet-based microfluidics is a subcategory of microfluidics in contrast with 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.{{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 }} Exploiting the benefits of droplet-based microfluidics efficiently requires a deep understanding of droplet generation to perform various logical operations{{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 }}{{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 }} such as droplet manipulation,{{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 }} droplet sorting,{{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 }} droplet merging,{{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 }} and droplet breakup.{{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 }} [39] => [40] => ===Digital microfluidics=== [41] => [42] => {{Main|Digital microfluidics}} [43] => Alternatives to the above closed-channel continuous-flow systems include novel open structures, where discrete, independently controllable droplets [44] => 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.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. The "fluid transistor" pioneered by Cytonix[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] also played a role. The technology was subsequently commercialised by Duke University. By using discrete unit-volume droplets,{{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 }} 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]]).{{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}} Many lab-on-a-chip applications have been demonstrated within the digital microfluidics paradigm using electrowetting. However, recently other techniques for droplet manipulation have also been demonstrated using magnetic force,{{cite journal | vauthors = Zhang Y, Nguyen NT | title = Magnetic digital microfluidics – a review | journal = Lab on a Chip | volume = 17 | issue = 6 | pages = 994–1008 | date = March 2017 | pmid = 28220916 | doi = 10.1039/c7lc00025a | s2cid = 5013542 | hdl = 10072/344389 | hdl-access = free }} [[surface acoustic wave]]s,{{cite journal | vauthors = Shilton RJ, Travagliati M, Beltram F, Cecchini M | title = Nanoliter-droplet acoustic streaming via ultra high frequency surface acoustic waves | journal = Advanced Materials | volume = 26 | issue = 29 | pages = 4941–4946 | date = August 2014 | pmid = 24677370 | pmc = 4173126 | doi = 10.1002/adma.201400091 | bibcode = 2014AdM....26.4941S }} [[optoelectrowetting]], mechanical actuation,{{cite journal | vauthors = Shemesh J, Bransky A, Khoury M, Levenberg S | title = Advanced microfluidic droplet manipulation based on piezoelectric actuation | journal = Biomedical Microdevices | volume = 12 | issue = 5 | pages = 907–914 | date = October 2010 | pmid = 20559875 | doi = 10.1007/s10544-010-9445-y | s2cid = 5298534 }} etc. [45] => [46] => === Paper-based microfluidics === [47] => {{Main|Paper-based microfluidics}} [48] => Paper-based microfluidic devices fill a growing niche for portable, cheap, and user-friendly medical diagnostic systems.{{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}} [49] => Paper based microfluidics rely on the phenomenon of capillary penetration in porous media.{{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 }} 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.{{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}} Paper-based microfluidics are considered as portable point-of-care biosensors used in a remote setting where advanced medical diagnostic tools are not accessible.{{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 }} Current applications include portable glucose detection{{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 }} and environmental testing,{{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}} with hopes of reaching areas that lack advanced medical diagnostic tools. [50] => [51] => === Particle detection microfluidics === [52] => One application area that has seen significant academic effort and some commercial effort is in the area of particle detection in fluids. Particle detection of small fluid-borne particles down to about 1 μm in diameter is typically done 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,{{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 }} and the implementation first described in Coulter's original patent.{{cite patent|country=US|number=2656508|status=|title=Means for counting particles suspended in a fluid|pubdate=Oct. 20, 1953|inventor=Wallace H. Coulter}} This is the method used to e.g. size and count erythrocytes (red blood cells [wiki]) 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}} [53] => [54] => 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 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 nm, with a concomitant reduction in the minimum particle diameters by several orders of magnitude. [55] => [56] => As a result, there has been some university-based development of microfluidic particle counting and sizing{{cite journal | vauthors = Kasianowicz JJ, Brandin E, Branton D, Deamer DW | title = Characterization of individual polynucleotide molecules using a membrane channel | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 24 | pages = 13770–13773 | date = November 1996 | pmid = 8943010 | pmc = 19421 | doi = 10.1073/pnas.93.24.13770 | doi-access = free | bibcode = 1996PNAS...9313770K }}{{cite journal | vauthors = Li J, Gershow M, Stein D, Brandin E, Golovchenko JA | title = DNA molecules and configurations in a solid-state nanopore microscope | journal = Nature Materials | volume = 2 | issue = 9 | pages = 611–615 | date = September 2003 | pmid = 12942073 | doi = 10.1038/nmat965 | s2cid = 7521907 | bibcode = 2003NatMa...2..611L | url = http://nrs.harvard.edu/urn-3:HUL.InstRepos:27877632 }}{{cite journal | vauthors = Uram JD, Ke K, Hunt AJ, Mayer M | title = Label-free affinity assays by rapid detection of immune complexes in submicrometer pores | journal = Angewandte Chemie | volume = 45 | issue = 14 | pages = 2281–2285 | date = March 2006 | pmid = 16506296 | doi = 10.1002/anie.200502862 | hdl = 2027.42/50668 | hdl-access = free }}{{cite journal| vauthors = Saleh O, Sohn LL |title=An artificial nanopore for molecular sensing|journal=Nano Lett.|date=2003|volume=3|issue=1|pages=37–38|doi=10.1021/nl0255202|bibcode=2003NanoL...3...37S }}{{cite journal | vauthors = Sen YH, Karnik R | title = Investigating the translocation of lambda-DNA molecules through PDMS nanopores | journal = Analytical and Bioanalytical Chemistry | volume = 394 | issue = 2 | pages = 437–446 | date = May 2009 | pmid = 19050856 | doi = 10.1007/s00216-008-2529-3 | s2cid = 7442686 | hdl = 1721.1/51892 }}{{cite journal | vauthors = Lewpiriyawong N, Kandaswamy K, Yang C, Ivanov V, Stocker R | title = Microfluidic characterization and continuous separation of cells and particles using conducting poly(dimethyl siloxane) electrode induced alternating current-dielectrophoresis | journal = Analytical Chemistry | volume = 83 | issue = 24 | pages = 9579–9585 | date = December 2011 | pmid = 22035423 | doi = 10.1021/ac202137y }}{{cite journal | vauthors = Rickel JM, Dixon AJ, Klibanov AL, Hossack JA | title = A flow focusing microfluidic device with an integrated Coulter particle counter for production, counting and size characterization of monodisperse microbubbles | journal = Lab on a Chip | volume = 18 | issue = 17 | pages = 2653–2664 | date = August 2018 | pmid = 30070301 | pmc = 6566100 | doi = 10.1039/C8LC00496J }}{{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 }}{{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 }}{{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 }} {{excessive citations inline|date=June 2023}}with the accompanying commercialization of this technology. This method has been termed microfluidic [[resistive pulse sensing]] (MRPS). [57] => [58] => === Microfluidic-assisted magnetophoresis === [59] => One major area of application for microfluidic devices is the separation and sorting of different fluids or cell types. Recent developments in the microfluidics field have seen the integration of microfluidic devices with [[wiktionary:magnetophoresis|magnetophoresis]]: the migration of particles by a [[magnetic field]].{{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 }} 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.{{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}} 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. [60] => [61] => Other, more research-oriented applications of microfluidic-assisted magnetophoresis are numerous and are generally targeted towards [[Cell (biology)|cell]] separation. The general way this is accomplished involves several steps. First, a paramagnetic substance (usually micro/[[nanoparticle]]s or a [[Ferrofluid|paramagnetic fluid]]){{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 }} 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]].{{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 }}{{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 }}{{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 }}{{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 }} 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. [62] => [63] => 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. 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.{{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}}{{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}} 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. [64] => [65] => ==Key application areas== [66] => [67] => Microfluidic structures include micropneumatic systems, i.e. microsystems for the handling of off-chip fluids (liquid pumps, gas valves, etc.), and microfluidic structures for the on-chip handling of nanoliter (nl) and picoliter (pl) volumes.{{cite book|vauthors = Nguyen NT, Wereley S|title=Fundamentals and Applications of Microfluidics|year=2006|publisher =[[Artech House]] }} To date, the most successful commercial application of microfluidics is the [[Inkjet printer|inkjet printhead]].{{cite journal | vauthors = DeMello AJ | title = Control and detection of chemical reactions in microfluidic systems | journal = Nature | volume = 442 | issue = 7101 | pages = 394–402 | date = July 2006 | pmid = 16871207 | doi = 10.1038/nature05062 | s2cid = 4421580 | bibcode = 2006Natur.442..394D }} Additionally, microfluidic manufacturing advances mean that makers can produce the devices in low-cost plastics{{cite journal | vauthors = Pawell RS, Inglis DW, Barber TJ, Taylor RA | title = Manufacturing and wetting low-cost microfluidic cell separation devices | journal = Biomicrofluidics | volume = 7 | issue = 5 | pages = 56501 | year = 2013 | pmid = 24404077 | pmc = 3785532 | doi = 10.1063/1.4821315 }} and automatically verify part quality.{{cite journal|doi = 10.1007/s10404-014-1464-1|title = Automating microfluidic part verification|journal = Microfluidics and Nanofluidics|volume = 18|issue = 4|pages = 657–665|year = 2015 | vauthors = Pawell RS, Taylor RA, Morris KV, Barber TJ |s2cid = 96793921 }} [68] => [69] => Advances in microfluidics technology are revolutionizing [[molecular biology]] procedures for enzymatic analysis (e.g., [[glucose]] and [[lactic acid|lactate]] [[assay]]s), [[DNA]] analysis (e.g., [[polymerase chain reaction]] and high-throughput [[sequencing]]), [[proteomics]], and in chemical synthesis.{{cite journal | vauthors = Konda A, Morin SA | title = Flow-directed synthesis of spatially variant arrays of branched zinc oxide mesostructures | journal = Nanoscale | volume = 9 | issue = 24 | pages = 8393–8400 | date = June 2017 | pmid = 28604901 | doi = 10.1039/C7NR02655B }}{{cite journal | vauthors = Cheng JJ, Nicaise SM, Berggren KK, Gradečak S | title = Dimensional Tailoring of Hydrothermally Grown Zinc Oxide Nanowire Arrays | journal = Nano Letters | volume = 16 | issue = 1 | pages = 753–759 | date = January 2016 | pmid = 26708095 | doi = 10.1021/acs.nanolett.5b04625 | bibcode = 2016NanoL..16..753C }} The basic idea of microfluidic biochips is to integrate [[assay]] operations such as detection, as well as sample pre-treatment and sample preparation on one chip.{{cite book|vauthors = Herold KE|veditors = Rasooly A|year=2009|title=Lab-on-a-Chip Technology: Fabrication and Microfluidics|publisher=Caister Academic Press|isbn= 978-1-904455-46-2}}{{cite book|vauthors = Herold KE|veditors = Rasooly A|year=2009|title=Lab-on-a-Chip Technology: Biomolecular Separation and Analysis|publisher=Caister Academic Press|isbn= 978-1-904455-47-9}} [70] => [71] => An emerging application area for biochips is [[clinical pathology]], especially the immediate [[point-of-care]] diagnosis of [[diseases]].{{cite journal | vauthors = Barrett MP, Cooper JM, Regnault C, Holm SH, Beech JP, Tegenfeldt JO, Hochstetter A | title = Microfluidics-Based Approaches to the Isolation of African Trypanosomes | journal = Pathogens | volume = 6 | issue = 4 | pages = 47 | date = October 2017 | pmid = 28981471 | pmc = 5750571 | doi = 10.3390/pathogens6040047 | doi-access = free }} In addition, microfluidics-based devices, capable of continuous sampling and real-time testing of air/water samples for biochemical [[toxins]] and other dangerous [[pathogens]],{{cite journal|vauthors = Jing G, Polaczyk A, Oerther DB, Papautsky I|title = Development of a microfluidic biosensor for detection of environmental mycobacteria|journal = Sensors and Actuators B: Chemical|volume = 123|issue = 1|pages = 614–621|date = 2007|doi = 10.1016/j.snb.2006.07.029 }} can serve as an always-on [[smoke alarm|"bio-smoke alarm"]] for early warning. [72] => [73] => Microfluidic technology has led to the creation of powerful tools for biologists to control the complete cellular environment, leading to new questions and discoveries. Many diverse advantages of this technology for microbiology are listed below: [74] => * General single cell studies including growth [75] => * Cellular aging: microfluidic devices such as the "mother machine" allow tracking of thousands of individual cells for many generations until they die{{cite journal | vauthors = Wang P, Robert L, Pelletier J, Dang WL, Taddei F, Wright A, Jun S | title = Robust growth of Escherichia coli | journal = Current Biology | volume = 20 | issue = 12 | pages = 1099–1103 | date = June 2010 | pmid = 20537537 | pmc = 2902570 | doi = 10.1016/j.cub.2010.04.045 }} [76] => * Microenvironmental control: ranging from mechanical environment{{cite journal | vauthors = Manbachi A, Shrivastava S, Cioffi M, Chung BG, Moretti M, Demirci U, Yliperttula M, Khademhosseini A | display-authors = 6 | title = Microcirculation within grooved substrates regulates cell positioning and cell docking inside microfluidic channels | journal = Lab on a Chip | volume = 8 | issue = 5 | pages = 747–754 | date = May 2008 | pmid = 18432345 | pmc = 2668874 | doi = 10.1039/B718212K }} to chemical environment{{cite journal | vauthors = Yliperttula M, Chung BG, Navaladi A, Manbachi A, Urtti A | title = High-throughput screening of cell responses to biomaterials | journal = European Journal of Pharmaceutical Sciences | volume = 35 | issue = 3 | pages = 151–160 | date = October 2008 | pmid = 18586092 | doi = 10.1016/j.ejps.2008.04.012 }}{{cite journal | vauthors = Gilbert DF, Mofrad SA, Friedrich O, Wiest J | title = Proliferation characteristics of cells cultured under periodic versus static conditions | journal = Cytotechnology | volume = 71 | issue = 1 | pages = 443–452 | date = February 2019 | pmid = 30515656 | pmc = 6368509 | doi = 10.1007/s10616-018-0263-z }} [77] => * Precise spatiotemporal concentration gradients by incorporating multiple chemical inputs to a single device{{cite journal | vauthors = Chung BG, Manbachi A, Saadi W, Lin F, Jeon NL, Khademhosseini A | title = A gradient-generating microfluidic device for cell biology | journal = Journal of Visualized Experiments | volume = 7 | issue = 7 | pages = 271 | year = 2007 | pmid = 18989442 | pmc = 2565846 | doi = 10.3791/271 }} [78] => * Force measurements of adherent cells or confined chromosomes: objects trapped in a microfluidic device can be directly manipulated using [[optical tweezers]] or other force-generating methods{{cite journal | vauthors = Pelletier J, Halvorsen K, Ha BY, Paparcone R, Sandler SJ, Woldringh CL, Wong WP, Jun S | display-authors = 6 | title = Physical manipulation of the Escherichia coli chromosome reveals its soft nature | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 40 | pages = E2649–E2656 | date = October 2012 | pmid = 22984156 | pmc = 3479577 | doi = 10.1073/pnas.1208689109 | doi-access = free | bibcode = 2012PNAS..109E2649P }} [79] => * Confining cells and exerting controlled forces by coupling with external force-generation methods such as [[Stokes flow]], [[optical tweezer]], or controlled deformation of the PDMS ([[Polydimethylsiloxane]]) device{{cite journal | vauthors = Amir A, Babaeipour F, McIntosh DB, Nelson DR, Jun S | title = Bending forces plastically deform growing bacterial cell walls | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 16 | pages = 5778–5783 | date = April 2014 | pmid = 24711421 | pmc = 4000856 | doi = 10.1073/pnas.1317497111 | arxiv = 1305.5843 | doi-access = free | bibcode = 2014PNAS..111.5778A }}{{cite journal | vauthors = Choi JW, Rosset S, Niklaus M, Adleman JR, Shea H, Psaltis D | title = 3-dimensional electrode patterning within a microfluidic channel using metal ion implantation | journal = Lab on a Chip | volume = 10 | issue = 6 | pages = 783–788 | date = March 2010 | pmid = 20221568 | doi = 10.1039/B917719A | url = https://authors.library.caltech.edu/17871/ }} [80] => * Electric field integration [81] => * Plant on a chip and plant tissue culture{{cite journal|vauthors = Yetisen AK, Jiang L, Cooper JR, Qin Y, Palanivelu R, Zohar Y|s2cid=12989263|title=A microsystem-based assay for studying pollen tube guidance in plant reproduction.|journal= J. Micromech. Microeng.|volume=25|issue= 5|pages= 054018|date=May 2011|doi= 10.1088/0960-1317/21/5/054018|bibcode=2011JMiMi..21e4018Y }} [82] => * Antibiotic resistance: microfluidic devices can be used as heterogeneous environments for microorganisms. In a heterogeneous environment, it is easier for a microorganism to evolve. This can be useful for testing the acceleration of evolution of a microorganism / for testing the development of antibiotic resistance. [83] => [84] => Some of these areas are further elaborated in the sections below: [85] => [86] => ===DNA chips (microarrays)=== [87] => [88] => Early biochips were based on the idea of a [[DNA microarray]], e.g., the GeneChip DNAarray from [[Affymetrix]], which is a piece of glass, plastic or silicon substrate, on which pieces of DNA (probes) are affixed in a microscopic array. Similar to a [[DNA microarray]], a [[protein array]] is a miniature array where a multitude of different capture agents, most frequently monoclonal [[antibodies]], are deposited on a chip surface; they are used to determine the presence and/or amount of [[protein]]s in biological samples, e.g., [[blood]]. A drawback of [[DNA]] and [[protein array]]s is that they are neither reconfigurable nor [[scalable]] after manufacture. [[Digital microfluidics]] has been described as a means for carrying out [[Digital PCR]]. [89] => [90] => ===Molecular biology=== [91] => In addition to microarrays, biochips have been designed for two-dimensional [[electrophoresis]],{{cite book|vauthors = Fan H, Das C, Chen H|veditors = Herold KE, Rasooly A|year=2009|chapter=Two-Dimensional Electrophoresis in a Chip|title=Lab-on-a-Chip Technology: Biomolecular Separation and Analysis|publisher=Caister Academic Press|isbn= 978-1-904455-47-9 }} [[transcriptome]] analysis,{{cite book|vauthors = Bontoux N, Dauphinot L, Potier MC|veditors = Herold KE, Rasooly A|year=2009|chapter=Elaborating Lab-on-a-Chips for Single-cell Transcriptome Analysis|title=Lab-on-a-Chip Technology: Biomolecular Separation and Analysis|publisher=Caister Academic Press|isbn= 978-1-904455-47-9 }} and [[Polymerase chain reaction|PCR]] amplification.{{cite book|vauthors = Cady NC|year=2009|chapter=Microchip-based PCR Amplification Systems|title=Lab-on-a-Chip Technology: Biomolecular Separation and Analysis|publisher=Caister Academic Press|isbn= 978-1-904455-47-9}} Other applications include various electrophoresis and [[liquid chromatography]] applications for proteins and [[DNA]], cell separation, in particular, blood cell separation, protein analysis, cell manipulation and analysis including cell viability analysis and [[microorganism]] capturing. [92] => [93] => ===Evolutionary biology=== [94] => [95] => By combining microfluidics with [[landscape ecology]] and [[nanofluidics]], a nano/micro fabricated fluidic landscape can be constructed by building local patches of [[bacterial]] [[habitat]] and connecting them by dispersal corridors. The resulting landscapes can be used as physical implementations of an [[adaptive landscape]],{{cite journal | vauthors = Keymer JE, Galajda P, Muldoon C, Park S, Austin RH | title = Bacterial metapopulations in nanofabricated landscapes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 46 | pages = 17290–17295 | date = November 2006 | pmid = 17090676 | pmc = 1635019 | doi = 10.1073/pnas.0607971103 | doi-access = free | bibcode = 2006PNAS..10317290K }} by generating a spatial mosaic of patches of opportunity distributed in space and time. The patchy nature of these fluidic landscapes allows for the study of adapting bacterial cells in a [[metapopulation]] system. The [[evolutionary ecology]] of these bacterial systems in these synthetic ecosystems allows for using [[biophysics]] to address questions in [[evolutionary biology]]. [96] => [97] => ===Cell behavior=== [98] => {{Main|Microfluidic cell culture}} [99] => The ability to create precise and carefully controlled [[chemoattractant]] gradients makes microfluidics the ideal tool to study motility,{{cite journal | vauthors = Hochstetter A, Stellamanns E, Deshpande S, Uppaluri S, Engstler M, Pfohl T | title = Microfluidics-based single cell analysis reveals drug-dependent motility changes in trypanosomes | journal = Lab on a Chip | volume = 15 | issue = 8 | pages = 1961–1968 | date = April 2015 | pmid = 25756872 | doi = 10.1039/C5LC00124B | url = https://edoc.unibas.ch/41485/1/C5LC00124B.pdf }} [[chemotaxis]] and the ability to evolve / develop resistance to antibiotics in small populations of microorganisms and in a short period of time. These microorganisms including [[bacteria]]{{cite journal | vauthors = Ahmed T, Shimizu TS, Stocker R | title = Microfluidics for bacterial chemotaxis | journal = Integrative Biology | volume = 2 | issue = 11–12 | pages = 604–629 | date = November 2010 | pmid = 20967322 | doi = 10.1039/C0IB00049C | hdl = 1721.1/66851 }} and the broad range of organisms that form the marine [[microbial loop]],{{cite journal | vauthors = Seymour JR, Simó R, Ahmed T, Stocker R | title = Chemoattraction to dimethylsulfoniopropionate throughout the marine microbial food web | journal = Science | volume = 329 | issue = 5989 | pages = 342–345 | date = July 2010 | pmid = 20647471 | doi = 10.1126/science.1188418 | s2cid = 12511973 | bibcode = 2010Sci...329..342S }} responsible for regulating much of the oceans' biogeochemistry. [100] => [101] => Microfluidics has also greatly aided the study of [[durotaxis]] by facilitating the creation of durotactic (stiffness) gradients. [102] => [103] => ===Cellular biophysics=== [104] => [105] => By rectifying the motion of individual swimming bacteria,{{cite journal | vauthors = Galajda P, Keymer J, Chaikin P, Austin R | title = A wall of funnels concentrates swimming bacteria | journal = Journal of Bacteriology | volume = 189 | issue = 23 | pages = 8704–8707 | date = December 2007 | pmid = 17890308 | pmc = 2168927 | doi = 10.1128/JB.01033-07 }} microfluidic structures can be used to extract mechanical motion from a population of motile bacterial cells.{{cite journal | vauthors = Angelani L, Di Leonardo R, Ruocco G | title = Self-starting micromotors in a bacterial bath | journal = Physical Review Letters | volume = 102 | issue = 4 | pages = 048104 | date = January 2009 | pmid = 19257480 | doi = 10.1103/PhysRevLett.102.048104 | arxiv = 0812.2375 | s2cid = 33943502 | bibcode = 2009PhRvL.102d8104A }} This way, bacteria-powered rotors can be built.{{cite journal | vauthors = Di Leonardo R, Angelani L, Dell'arciprete D, Ruocco G, Iebba V, Schippa S, Conte MP, Mecarini F, De Angelis F, Di Fabrizio E | display-authors = 6 | title = Bacterial ratchet motors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 21 | pages = 9541–9545 | date = May 2010 | pmid = 20457936 | pmc = 2906854 | doi = 10.1073/pnas.0910426107 | arxiv = 0910.2899 | doi-access = free | bibcode = 2010PNAS..107.9541D }}{{cite journal | vauthors = Sokolov A, Apodaca MM, Grzybowski BA, Aranson IS | title = Swimming bacteria power microscopic gears | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 3 | pages = 969–974 | date = January 2010 | pmid = 20080560 | pmc = 2824308 | doi = 10.1073/pnas.0913015107 | doi-access = free | bibcode = 2010PNAS..107..969S }} [106] => [107] => ===Optics=== [108] => The merger of microfluidics and optics is typical known as [[optofluidics]]. Examples of optofluidic devices are tunable microlens arrays{{cite journal | vauthors = Grilli S, Miccio L, Vespini V, Finizio A, De Nicola S, Ferraro P | title = Liquid micro-lens array activated by selective electrowetting on lithium niobate substrates | journal = Optics Express | volume = 16 | issue = 11 | pages = 8084–8093 | date = May 2008 | pmid = 18545521 | doi = 10.1364/OE.16.008084 | s2cid = 15923737 | bibcode = 2008OExpr..16.8084G | doi-access = free }}{{cite journal|doi = 10.1364/OPN.19.12.000034|title = Manipulating Thin Liquid Films for Tunable Microlens Arrays|journal = Optics and Photonics News|volume = 19|issue = 12|pages = 34|year = 2008| vauthors = Ferraro P, Miccio L, Grilli S, Finizio A, De Nicola S, Vespini V }} and optofluidic microscopes. [109] => [110] => Microfluidic flow enables fast sample throughput, automated imaging of large sample populations, as well as 3D capabilities.{{cite journal | vauthors = Pégard NC, Toth ML, Driscoll M, Fleischer JW | title = Flow-scanning optical tomography | journal = Lab on a Chip | volume = 14 | issue = 23 | pages = 4447–4450 | date = December 2014 | pmid = 25256716 | pmc = 5859944 | doi = 10.1039/C4LC00701H }}{{cite book|doi = 10.1364/BIOMED.2012.BM4B.4|chapter = 3D microfluidic microscopy using a tilted channel|title = Biomedical Optics and 3-D Imaging|pages = BM4B.4|year = 2012| vauthors = Pégard NC, Fleischer JW |isbn = 978-1-55752-942-8}} or superresolution.{{cite journal| vauthors = Lu CH, Pégard NC, Fleischer JW |title=Flow-based structured illumination|journal=Applied Physics Letters|date=22 April 2013 |volume=102 |issue=16 |pages=161115|doi=10.1063/1.4802091|bibcode=2013ApPhL.102p1115L }} [111] => [112] => === Photonics Lab on a Chip (PhLOC) === [113] => Due to the increase in safety concerns and operating costs of common analytic methods ([[Inductively coupled plasma mass spectrometry|ICP-MS]], [[Inductively coupled plasma atomic emission spectroscopy|ICP-AAS]], and [[Inductively coupled plasma atomic emission spectroscopy|ICP-OES]]{{Cite journal |last1=Kirsanov |first1=D. |last2=Babain |first2=V. |last3=Agafonova-Moroz |first3=M. |last4=Lumpov |first4=A. |last5=Legin |first5=A. |date=2012-03-01 |title=Combination of optical spectroscopy and chemometric techniques—a possible way for on-line monitoring of spent nuclear fuel (SNF) reprocessing |url=https://www.degruyter.com/document/doi/10.1524/ract.2012.1901/html |journal=Radiochimica Acta |language=en |volume=100 |issue=3 |pages=185–188 |doi=10.1524/ract.2012.1901|s2cid=101475605 }}), the Photonics Lab on a Chip (PhLOC) is becoming an increasingly popular tool for the analysis of actinides and nitrates in spent nuclear waste. The PhLOC is based on the simultaneous application of [[Raman spectroscopy|Raman]] and [[Ultraviolet–visible spectroscopy|UV-Vis-NIR]] spectroscopy,{{Cite journal |last1=Nelson |first1=Gilbert L. |last2=Lackey |first2=Hope E. |last3=Bello |first3=Job M. |last4=Felmy |first4=Heather M. |last5=Bryan |first5=Hannah B. |last6=Lamadie |first6=Fabrice |last7=Bryan |first7=Samuel A. |last8=Lines |first8=Amanda M. |date=2021-01-26 |title=Enabling Microscale Processing: Combined Raman and Absorbance Spectroscopy for Microfluidic On-Line Monitoring |url=https://pubs.acs.org/doi/10.1021/acs.analchem.0c04225 |journal=Analytical Chemistry |language=en |volume=93 |issue=3 |pages=1643–1651 |doi=10.1021/acs.analchem.0c04225 |pmid=33337856 |osti=1783814 |s2cid=229323758 |issn=0003-2700}} which allows for the analysis of more complex mixtures which contain several actinides at different oxidation states.{{Cite journal |last1=Mattio |first1=Elodie |last2=Caleyron |first2=Audrey |last3=Miguirditchian |first3=Manuel |last4=Lines |first4=Amanda M. |last5=Bryan |first5=Samuel A. |last6=Lackey |first6=Hope E. |last7=Rodriguez-Ruiz |first7=Isaac |last8=Lamadie |first8=Fabrice |date=May 2022 |title=Microfluidic In-Situ Spectrophotometric Approaches to Tackle Actinides Analysis in Multiple Oxidation States |url=http://journals.sagepub.com/doi/10.1177/00037028211063916 |journal=Applied Spectroscopy |language=en |volume=76 |issue=5 |pages=580–589 |doi=10.1177/00037028211063916 |pmid=35108115 |bibcode=2022ApSpe..76..580M |s2cid=246488502 |issn=0003-7028 |via=Sage Journals}} Measurements made with these methods have been validated at the bulk level for industrial tests,{{Cite journal |last1=Bryan |first1=S. A. |last2=Levitskaia |first2=Tatiana G. |last3=Johnsen |first3=A. M. |last4=Orton |first4=C. R. |last5=Peterson |first5=J. M. |date=September 2011 |title=Spectroscopic monitoring of spent nuclear fuel reprocessing streams: an evaluation of spent fuel solutions via Raman, visible, and near-infrared spectroscopy |url=https://www.degruyter.com/document/doi/10.1524/ract.2011.1865/html |journal=Radiochimica Acta |language=en |volume=99 |issue=9 |pages=563–572 |doi=10.1524/ract.2011.1865 |s2cid=95632074 |issn=0033-8230}} and are observed to have a much lower variance at the micro-scale.{{Cite journal |last1=Nelson |first1=Gilbert L. |last2=Lines |first2=Amanda M. |last3=Bello |first3=Job M. |last4=Bryan |first4=Samuel A. |date=2019-09-27 |title=Online Monitoring of Solutions Within Microfluidic Chips: Simultaneous Raman and UV–Vis Absorption Spectroscopies |url=https://pubs.acs.org/doi/10.1021/acssensors.9b00736 |journal=ACS Sensors |language=en |volume=4 |issue=9 |pages=2288–2295 |doi=10.1021/acssensors.9b00736 |pmid=31434479 |s2cid=201275176 |issn=2379-3694}} This approach has been found to have molar extinction coefficients (UV-Vis) in line with known literature values over a comparatively large concentration span for 150 μL via elongation of the measurement channel, and obeys [[Beer–Lambert law|Beer's Law]] at the micro-scale for U(IV).{{Cite journal |last1=Rodríguez-Ruiz |first1=Isaac |last2=Lamadie |first2=Fabrice |last3=Charton |first3=Sophie |date=2018-02-20 |title=Uranium(VI) On-Chip Microliter Concentration Measurements in a Highly Extended UV–Visible Absorbance Linearity Range |url=https://pubs.acs.org/doi/10.1021/acs.analchem.7b05162 |journal=Analytical Chemistry |language=en |volume=90 |issue=4 |pages=2456–2460 |doi=10.1021/acs.analchem.7b05162 |pmid=29327582 |issn=0003-2700}} Through the development of a spectrophotometric approach to analyzing spent fuel, an on-line method for measurement of reactant quantities is created, increasing the rate at which samples can be analyzed and thus decreasing the size of deviations detectable within reprocessing. [114] => [115] => Through the application of the PhLOC, flexibility and safety of operational methods are increased. Since the analysis of spent nuclear fuel involves extremely harsh conditions, the application of disposable and rapidly produced devices (Based on castable and/or engravable materials such as PDMS, PMMA, and glass{{Cite journal |last1=Mattio |first1=Elodie |last2=Lamadie |first2=Fabrice |last3=Rodriguez-Ruiz |first3=Isaac |last4=Cames |first4=Beatrice |last5=Charton |first5=Sophie |date=2020-02-01 |title=Photonic Lab-on-a-Chip analytical systems for nuclear applications: optical performance and UV–Vis–IR material characterization after chemical exposure and gamma irradiation |url=https://doi.org/10.1007/s10967-019-06992-x |journal=Journal of Radioanalytical and Nuclear Chemistry |language=en |volume=323 |issue=2 |pages=965–973 |doi=10.1007/s10967-019-06992-x |s2cid=209441127 |issn=1588-2780}}) is advantageous, although material integrity must be considered under specific harsh conditions. Through the usage of fiber optic coupling, the device can be isolated from instrumentation, preventing irradiative damage and minimizing the exposure of lab personnel to potentially harmful radiation, something not possible on the lab scale nor with the previous standard of analysis. The shrinkage of the device also allows for lower amounts of analyte to be used, decreasing the amount of waste generated and exposure to hazardous materials. [116] => [117] => Expansion of the PhLOC to miniaturize research of the full nuclear fuel cycle is currently being evaluated, with steps of the [[PUREX]] process successfully being demonstrated at the micro-scale. Likewise, the microfluidic technology developed for the analysis of spent nuclear fuel is predicted to expand horizontally to analysis of other actinide, lanthanides, and transition metals with little to no modification. [118] => [119] => === High Performance Liquid Chromatography (HPLC) === [120] => HPLC in the field of microfluidics comes in two different forms. Early designs included running liquid through the HPLC column then transferring the eluted liquid to microfluidic chips and attaching HPLC columns to the microfluidic chip directly.{{cite journal | vauthors = Kim JY, Cho SW, Kang DK, Edel JB, Chang SI, deMello AJ, O'Hare D | title = Lab-chip HPLC with integrated droplet-based microfluidics for separation and high frequency compartmentalisation | journal = Chemical Communications | volume = 48 | issue = 73 | pages = 9144–9146 | date = September 2012 | pmid = 22871959 | doi = 10.1039/c2cc33774f }} The early methods had the advantage of easier detection from certain machines like those that measure fluorescence.{{cite journal | vauthors = Ochoa A, Álvarez-Bohórquez E, Castillero E, Olguin LF | title = Detection of Enzyme Inhibitors in Crude Natural Extracts Using Droplet-Based Microfluidics Coupled to HPLC | journal = Analytical Chemistry | volume = 89 | issue = 9 | pages = 4889–4896 | date = May 2017 | pmid = 28374582 | doi = 10.1021/acs.analchem.6b04988 }} More recent designs have fully integrated HPLC columns into microfluidic chips. The main advantage of integrating HPLC columns into microfluidic devices is the smaller form factor that can be achieved, which allows for additional features to be combined within one microfluidic chip. Integrated chips can also be fabricated from multiple different materials, including glass and polyimide which are quite different from the standard material of [[Polydimethylsiloxane|PDMS]] used in many different droplet-based microfluidic devices.{{cite journal | vauthors = Gerhardt RF, Peretzki AJ, Piendl SK, Belder D | title = Seamless Combination of High-Pressure Chip-HPLC and Droplet Microfluidics on an Integrated Microfluidic Glass Chip | journal = Analytical Chemistry | volume = 89 | issue = 23 | pages = 13030–13037 | date = December 2017 | pmid = 29096060 | doi = 10.1021/acs.analchem.7b04331 }}{{cite conference|vauthors = Killeen K, Yin H, Sobek D, Brennen R, Van de Goor T|title = Chip-LC/MS: HPLC-MS using polymer microfluidics.|journal = Proc MicroTAS|conference = 7th lnternatonal Conference on Miniaturized Chemical and Blochemlcal Analysts Systems|location = Squaw Valley, Callfornla USA|date = October 2003|pages = 481–484|url = https://www.rsc.org/binaries/LOC/2003/Volume1/120-376.pdf }} This is an important feature because different applications of HPLC microfluidic chips may call for different pressures. PDMS fails in comparison for high-pressure uses compared to glass and polyimide. High versatility of HPLC integration ensures robustness by avoiding connections and fittings between the column and chip.{{cite journal | vauthors = Vollmer M, Hörth P, Rozing G, Couté Y, Grimm R, Hochstrasser D, Sanchez JC | title = Multi-dimensional HPLC/MS of the nucleolar proteome using HPLC-chip/MS | journal = Journal of Separation Science | volume = 29 | issue = 4 | pages = 499–509 | date = March 2006 | pmid = 16583688 | doi = 10.1002/jssc.200500334 }} The ability to build off said designs in the future allows the field of microfluidics to continue expanding its potential applications. [121] => [122] => The potential applications surrounding integrated HPLC columns within microfluidic devices have proven expansive over the last 10–15 years. The integration of such columns allows for experiments to be run where materials were in low availability or very expensive, like in biological analysis of proteins. This reduction in reagent volumes allows for new experiments like single-cell protein analysis, which due to size limitations of prior devices, previously came with great difficulty.{{cite journal | vauthors = Reichmuth DS, Shepodd TJ, Kirby BJ | title = Microchip HPLC of peptides and proteins | journal = Analytical Chemistry | volume = 77 | issue = 9 | pages = 2997–3000 | date = May 2005 | pmid = 15859622 | doi = 10.1021/ac048358r }} The coupling of HPLC-chip devices with other spectrometry methods like mass-spectrometry allow for enhanced confidence in identification of desired species, like proteins.{{cite journal | vauthors = Hardouin J, Duchateau M, Joubert-Caron R, Caron M | title = Usefulness of an integrated microfluidic device (HPLC-Chip-MS) to enhance confidence in protein identification by proteomics | journal = Rapid Communications in Mass Spectrometry | volume = 20 | issue = 21 | pages = 3236–3244 | date = 2006 | pmid = 17016832 | doi = 10.1002/rcm.2725 | bibcode = 2006RCMS...20.3236H }} Microfluidic chips have also been created with internal delay-lines that allow for gradient generation to further improve HPLC, which can reduce the need for further separations.{{cite journal | vauthors = Brennen RA, Yin H, Killeen KP | title = Microfluidic gradient formation for nanoflow chip LC | journal = Analytical Chemistry | volume = 79 | issue = 24 | pages = 9302–9309 | date = December 2007 | pmid = 17997523 | doi = 10.1021/ac0712805 }} Some other practical applications of integrated HPLC chips include the determination of drug presence in a person through their hair{{cite journal | vauthors = Zhu KY, Leung KW, Ting AK, Wong ZC, Ng WY, Choi RC, Dong TT, Wang T, Lau DT, Tsim KW | display-authors = 6 | title = Microfluidic chip based nano liquid chromatography coupled to tandem mass spectrometry for the determination of abused drugs and metabolites in human hair | journal = Analytical and Bioanalytical Chemistry | volume = 402 | issue = 9 | pages = 2805–2815 | date = March 2012 | pmid = 22281681 | doi = 10.1007/s00216-012-5711-6 | s2cid = 7748546 }} and the labeling of peptides through reverse phase liquid chromatography.{{cite journal | vauthors = Polat AN, Kraiczek K, Heck AJ, Raijmakers R, Mohammed S | title = Fully automated isotopic dimethyl labeling and phosphopeptide enrichment using a microfluidic HPLC phosphochip | journal = Analytical and Bioanalytical Chemistry | volume = 404 | issue = 8 | pages = 2507–2512 | date = November 2012 | pmid = 22975804 | doi = 10.1007/s00216-012-6395-7 | s2cid = 32545802 }} [123] => [124] => ===Acoustic droplet ejection (ADE)=== [125] => [126] => [[Acoustic droplet ejection]] uses a pulse of [[ultrasound]] to move low volumes of [[fluids]] (typically nanoliters or picoliters) without any physical contact. This technology focuses acoustic energy into a fluid sample to eject droplets as small as a millionth of a millionth of a litre (picoliter = 10−12 litre). ADE technology is a very gentle process, and it can be used to transfer proteins, high molecular weight DNA and live cells without damage or loss of viability. This feature makes the technology suitable for a wide variety of applications including [[proteomics]] and cell-based assays. [127] => [128] => ===Fuel cells=== [129] => {{Further|Electroosmotic pump}} [130] => Microfluidic [[fuel cells]] can use laminar flow to separate the fuel and its oxidant to control the interaction of the two fluids without the physical barrier that conventional fuel cells require.{{cite web| vauthors = Santiago JG |work = Stanford Microfluidics Laboratory|url = http://microfluidics.stanford.edu/fuel_cells.htm|title = Water Management in PEM Fuel Cells|archive-url = https://web.archive.org/web/20080628192632/http://microfluidics.stanford.edu/fuel_cells.htm|archive-date = 28 June 2008 }}{{cite journal| vauthors = Tretkoff E |date = May 2005|volume = 14|issue = 5|pages = 3|journal = APS News|url = http://www.aps.org/publications/apsnews/200505/fuel.cfm|title = Building a Better Fuel Cell Using Microfluidics }}{{cite web| vauthors = Allen J |url = http://www.me.mtu.edu/mnit/|title = Fuel Cell Initiative at MnIT Microfluidics Laboratory|publisher = Michigan Technological University|archive-url = https://web.archive.org/web/20080305215325/http://www.me.mtu.edu/mnit/|archive-date = 2008-03-05 }} [131] => [132] => === Astrobiology === [133] => To understand the prospects for life to exist elsewhere in the universe, [[Astrobiology|astrobiologists]] are interested in measuring the chemical composition of extraplanetary bodies.{{cite web|url=https://nai.nasa.gov/media/medialibrary/2015/10/NASA_Astrobiology_Strategy_2015_151008.pdf|title=NASA Astrobiology Strategy, 2015|archive-url=https://web.archive.org/web/20161222190306/https://nai.nasa.gov/media/medialibrary/2015/10/NASA_Astrobiology_Strategy_2015_151008.pdf|archive-date=2016-12-22|url-status=dead}} Because of their small size and wide-ranging functionality, microfluidic devices are uniquely suited for these remote sample analyses.{{cite journal | vauthors = Beebe DJ, Mensing GA, Walker GM | title = Physics and applications of microfluidics in biology | journal = Annual Review of Biomedical Engineering | volume = 4 | pages = 261–286 | date = 2002 | pmid = 12117759 | doi = 10.1146/annurev.bioeng.4.112601.125916 }}{{cite journal | vauthors = Theberge AB, Courtois F, Schaerli Y, Fischlechner M, Abell C, Hollfelder F, Huck WT | title = Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology | journal = Angewandte Chemie | volume = 49 | issue = 34 | pages = 5846–5868 | date = August 2010 | pmid = 20572214 | doi = 10.1002/anie.200906653 | s2cid = 18609389 | url = https://eprints.soton.ac.uk/340192/2/__soton.ac.uk_ude_personalfiles_users_jks1m11_mydesktop_theberge_2010_microdroplets%2520in%2520microfluidics-an%2520evolving%2520platform%2520for%2520discoveries%2520in%2520chemistry%2520and%2520biology.pdf }}{{cite journal | vauthors = van Dinther AM, Schroën CG, Vergeldt FJ, van der Sman RG, Boom RM | title = Suspension flow in microfluidic devices--a review of experimental techniques focussing on concentration and velocity gradients | journal = Advances in Colloid and Interface Science | volume = 173 | pages = 23–34 | date = May 2012 | pmid = 22405541 | doi = 10.1016/j.cis.2012.02.003 }} From an extraterrestrial sample, the organic content can be assessed using microchip [[capillary electrophoresis]] and selective fluorescent dyes.{{cite journal | vauthors = Mora MF, Greer F, Stockton AM, Bryant S, Willis PA | title = Toward total automation of microfluidics for extraterrestial [sic] in situ analysis | journal = Analytical Chemistry | volume = 83 | issue = 22 | pages = 8636–8641 | date = November 2011 | pmid = 21972965 | doi = 10.1021/ac202095k }} These devices are capable of detecting [[amino acid]]s,{{cite journal | vauthors = Chiesl TN, Chu WK, Stockton AM, Amashukeli X, Grunthaner F, Mathies RA | title = Enhanced amine and amino acid analysis using Pacific Blue and the Mars Organic Analyzer microchip capillary electrophoresis system | journal = Analytical Chemistry | volume = 81 | issue = 7 | pages = 2537–2544 | date = April 2009 | pmid = 19245228 | doi = 10.1021/ac8023334 }} [[peptide]]s,{{cite journal|vauthors = Kaiser RI, Stockton AM, Kim YS, Jensen EC, Mathies RA|date=2013|title=On the Formation of Dipeptides in Interstellar Model Ices|journal=The Astrophysical Journal|language=en|volume=765|issue=2|pages=111|doi=10.1088/0004-637X/765/2/111|issn=0004-637X|bibcode=2013ApJ...765..111K|s2cid=45120615 |doi-access=free}} [[fatty acid]]s,{{cite journal | vauthors = Stockton AM, Tjin CC, Chiesl TN, Mathies RA | title = Analysis of carbonaceous biomarkers with the Mars Organic Analyzer microchip capillary electrophoresis system: carboxylic acids | journal = Astrobiology | volume = 11 | issue = 6 | pages = 519–528 | date = July 2011 | pmid = 21790324 | doi = 10.1089/ast.2011.0634 | bibcode = 2011AsBio..11..519S }} and simple [[aldehyde]]s, [[ketone]]s,{{cite journal | vauthors = Stockton AM, Tjin CC, Huang GL, Benhabib M, Chiesl TN, Mathies RA | title = Analysis of carbonaceous biomarkers with the Mars Organic Analyzer microchip capillary electrophoresis system: aldehydes and ketones | journal = Electrophoresis | volume = 31 | issue = 22 | pages = 3642–3649 | date = November 2010 | pmid = 20967779 | doi = 10.1002/elps.201000424 | s2cid = 34503284 }} and [[thiol]]s.{{cite book|vauthors = Mora MF, Stockton AM, Willis PA|title = Microchip Capillary Electrophoresis Protocols|chapter = Analysis of thiols by microchip capillary electrophoresis for in situ planetary investigations|series = Methods in Molecular Biology|volume = 1274|pages = 43–52|date = 2015|pmid = 25673481|doi = 10.1007/978-1-4939-2353-3_4|publisher = Humana Press|location = New York, NY|isbn = 9781493923526 }} These analyses coupled together could allow powerful detection of the key components of life, and hopefully inform our search for functioning extraterrestrial life.{{cite journal|vauthors = Bowden SA, Wilson R, Taylor C, Cooper JM, Parnell J|date=January 2007|title=The extraction of intracrystalline biomarkers and other organic compounds from sulphate minerals using a microfluidic format – a feasibility study for remote fossil-life detection using a microfluidic H-cell|url=https://www.cambridge.org/core/journals/international-journal-of-astrobiology/article/the-extraction-of-intracrystalline-biomarkers-and-other-organic-compounds-from-sulphate-minerals-using-a-microfluidic-format-a-feasibility-study-for-remote-fossil-life-detection-using-a-microfluidic-h-cell/C66EB723687CB09F2DAB638A074CBA9D|journal=International Journal of Astrobiology|language=en|volume=6|issue=1|pages=27–36|doi=10.1017/S147355040600351X|issn=1475-3006|bibcode=2007IJAsB...6...27B|s2cid=123048038}} [134] => [135] => ===Food science=== [136] => Microfluidic techniques such as droplet microfluidics, paper microfluidics, and [[lab-on-a-chip]] are used in the realm of food science in a variety of categories.{{Cite journal|last1=Neethirajan|first1=Suresh|last2=Kobayashi|first2=Isao|last3=Nakajima|first3=Mitsutoshi|last4=Wu|first4=Dan|last5=Nandagopal|first5=Saravanan|last6=Lin|first6=Francis|date=2011|title=Microfluidics for food, agriculture and biosystems industries|url=http://xlink.rsc.org/?DOI=c0lc00230e|journal=Lab on a Chip|language=en|volume=11|issue=9|pages=1574–1586|doi=10.1039/c0lc00230e|pmid=21431239 |issn=1473-0197}} Research in nutrition,{{Cite journal|last1=Verma|first1=Kiran|last2=Tarafdar|first2=Ayon|last3=Badgujar|first3=Prarabdh C.|date=January 2021|title=Microfluidics assisted tragacanth gum based sub-micron curcumin suspension and its characterization|url=http://dx.doi.org/10.1016/j.lwt.2020.110269|journal=LWT|volume=135|pages=110269|doi=10.1016/j.lwt.2020.110269|s2cid=224875232 |issn=0023-6438}}{{Cite journal|last1=Hsiao|first1=Ching-Ju|last2=Lin|first2=Jui-Fen|last3=Wen|first3=Hsin-Yi|last4=Lin|first4=Yu-Mei|last5=Yang|first5=Chih-Hui|last6=Huang|first6=Keng-Shiang|last7=Shaw|first7=Jei-Fu|date=2020-02-15|title=Enhancement of the stability of chlorophyll using chlorophyll-encapsulated polycaprolactone microparticles based on droplet microfluidics|url=https://www.sciencedirect.com/science/article/pii/S0308814619314116|journal=Food Chemistry|language=en|volume=306|pages=125300|doi=10.1016/j.foodchem.2019.125300|pmid=31562927 |s2cid=201219877 |issn=0308-8146}} food processing, and food safety benefit from microfluidic technique because experiments can be done with less reagents. [137] => [138] => Food processing requires the ability to enable shelf stability in foods, such as emulsions or additions of preservatives. Techniques such as droplet microfluidics are used to create emulsions that are more controlled and complex than those created by traditional homogenization due to the precision of droplets that is achievable. Using microfluidics for emulsions is also more energy efficient compared to homogenization in which “only 5% of the supplied energy is used to generate the emulsion, with the rest dissipated as heat” .{{Cite journal|last1=He|first1=Shan|last2=Joseph|first2=Nikita|last3=Feng|first3=Shilun|last4=Jellicoe|first4=Matt|last5=Raston|first5=Colin L.|date=2020|title=Application of microfluidic technology in food processing|url=http://dx.doi.org/10.1039/d0fo01278e|journal=Food & Function|volume=11|issue=7|pages=5726–5737|doi=10.1039/d0fo01278e|pmid=32584365 |s2cid=220059922 |issn=2042-6496}} Although these methods have benefits, they currently lack the ability to be produced at large scale that is needed for commercialization.{{Cite journal|last1=Hinderink|first1=Emma B. A.|last2=Kaade|first2=Wael|last3=Sagis|first3=Leonard|last4=Schroën|first4=Karin|last5=Berton-Carabin|first5=Claire C.|date=2020-05-01|title=Microfluidic investigation of the coalescence susceptibility of pea protein-stabilised emulsions: Effect of protein oxidation level|url=https://www.sciencedirect.com/science/article/pii/S0268005X19317345|journal=Food Hydrocolloids|language=en|volume=102|pages=105610|doi=10.1016/j.foodhyd.2019.105610|s2cid=212935489 |issn=0268-005X|doi-access=free}} Microfluidics are also used in research as they allow for innovation in food chemistry and food processing. An example in food engineering research is a novel micro-3D-printed device fabricated to research production of droplets for potential food processing industry use, particularly in work with enhancing emulsions.{{Cite journal|last1=Zhang|first1=Jia|last2=Xu|first2=Wenhua|last3=Xu|first3=Fengying|last4=Lu|first4=Wangwang|last5=Hu|first5=Liuyun|last6=Zhou|first6=Jianlin|last7=Zhang|first7=Chen|last8=Jiang|first8=Zhuo|date=February 2021|title=Microfluidic droplet formation in co-flow devices fabricated by micro 3D printing|url=http://dx.doi.org/10.1016/j.jfoodeng.2020.110212|journal=Journal of Food Engineering|volume=290|pages=110212|doi=10.1016/j.jfoodeng.2020.110212|s2cid=224841971 |issn=0260-8774}} [139] => [140] => Paper and droplet microfluidics allow for devices that can detect small amounts of unwanted bacteria or chemicals, making them useful in food safety and analysis.Harmon JB, Gray HK, Young CC, Schwab KJ (2020) Microfluidic droplet application for bacterial surveillance in fresh-cut produce wash waters. PLoS ONE 15(6): e0233239. https://doi.org/10.1371/journal.pone.0233239 Paper-based microfluidic devices are often referred to as microfluidic paper-based analytical devices (µPADs) and can detect such things as nitrate,{{Cite journal|last1=Trofimchuk|first1=Evan|last2=Hu|first2=Yaxi|last3=Nilghaz|first3=Azadeh|last4=Hua|first4=Marti Z.|last5=Sun|first5=Selina|last6=Lu|first6=Xiaonan|date=2020-06-30|title=Development of paper-based microfluidic device for the determination of nitrite in meat|url=https://www.sciencedirect.com/science/article/pii/S0308814620302557|journal=Food Chemistry|language=en|volume=316|pages=126396|doi=10.1016/j.foodchem.2020.126396|pmid=32066068 |s2cid=211160645 |issn=0308-8146}} preservatives,{{Cite journal|last1=Ko|first1=Chien-Hsuan|last2=Liu|first2=Chan-Chiung|last3=Chen|first3=Kuan-Hong|last4=Sheu|first4=Fuu|last5=Fu|first5=Lung-Ming|last6=Chen|first6=Szu-Jui|date=2021-05-30|title=Microfluidic colorimetric analysis system for sodium benzoate detection in foods|url=https://www.sciencedirect.com/science/article/pii/S0308814620326352|journal=Food Chemistry|language=en|volume=345|pages=128773|doi=10.1016/j.foodchem.2020.128773|pmid=33302108 |s2cid=228100279 |issn=0308-8146}} or antibiotics{{Cite journal|last1=Trofimchuk|first1=Evan|last2=Nilghaz|first2=Azadeh|last3=Sun|first3=Selina|last4=Lu|first4=Xiaonan|date=2020|title=Determination of norfloxacin residues in foods by exploiting the coffee-ring effect and paper-based microfluidics device coupling with smartphone-based detection|url=https://onlinelibrary.wiley.com/doi/abs/10.1111/1750-3841.15039|journal=Journal of Food Science|language=en|volume=85|issue=3|pages=736–743|doi=10.1111/1750-3841.15039|pmid=32017096 |s2cid=211023292 |issn=1750-3841}} in meat by a colorimetric reaction that can be detected with a smartphone. These methods are being researched because they use less reactants, space, and time compared to traditional techniques such as liquid chromatography. µPADs also make home detection tests possible, which is of interest to those with allergies and intolerances. In addition to paper-based methods, research demonstrates droplet-based microfluidics shows promise in drastically shortening the time necessary to confirm viable bacterial contamination in agricultural waters in the domestic and international food industry. [141] => [142] => ===Future directions=== [143] => [144] => ==== Microfluidics for personalized cancer treatment ==== [145] => Personalized cancer treatment is a tuned method based on the patient's diagnosis and background. Microfluidic technology offers sensitive detection with higher throughput, as well as reduced time and costs. For personalized cancer treatment, tumor composition and drug sensitivities are very important.{{Cite journal| vauthors = Hajji I, Serra M, Geremie L, Ferrante I, Renault R, Viovy JL, Descroix S, Ferraro D |date=2020|title=Droplet microfluidic platform for fast and continuous-flow RT-qPCR analysis devoted to cancer diagnosis application |journal=Sensors and Actuators B: Chemical |volume=303 |pages=127171 |doi=10.1016/j.snb.2019.127171 |s2cid=208705450}} [146] => [147] => A patient's drug response can be predicted based on the status of [[biomarker]]s, or the severity and progression of the disease can be predicted based on the atypical presence of specific cells.{{cite journal | vauthors = Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA | display-authors = 6 | title = Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets | journal = Cell | volume = 161 | issue = 5 | pages = 1202–1214 | date = May 2015 | pmid = 26000488 | pmc = 4481139 | doi = 10.1016/j.cell.2015.05.002 }} [[Droplet-based microfluidics|Drop]]-[[qPCR]] is a [[Droplet-based microfluidics|droplet microfluidic]] technology in which droplets are transported in a reusable capillary and alternately flow through two areas maintained at different constant temperatures and fluorescence detection. It can be efficient with a low contamination risk to detect [[HER2/neu|Her2]]. A [[Digital microfluidics|digital]] droplet‐based [[Polymerase chain reaction|PCR]] method can be used to detect the [[KRAS]] mutations with [[TaqMan|TaqMan probes]], to enhance detection of the mutative gene ratio.{{cite journal | vauthors = Liu P, Liang H, Xue L, Yang C, Liu Y, Zhou K, Jiang X | title = Potential clinical significance of plasma-based KRAS mutation analysis using the COLD-PCR/TaqMan(®) -MGB probe genotyping method | journal = Experimental and Therapeutic Medicine | volume = 4 | issue = 1 | pages = 109–112 | date = July 2012 | pmid = 23060932 | pmc = 3460285 | doi = 10.3892/etm.2012.566 }} In addition, accurate prediction of postoperative disease progression in [[Breast cancer|breast]] or [[prostate cancer]] patients is essential for determining post-surgery treatment. A simple microfluidic chamber, coated with a carefully formulated extracellular matrix mixture is used for cells obtained from tumor [[biopsy]] after 72 hours of growth and a thorough evaluation of cells by imaging.{{cite journal | vauthors = Manak MS, Varsanik JS, Hogan BJ, Whitfield MJ, Su WR, Joshi N, Steinke N, Min A, Berger D, Saphirstein RJ, Dixit G, Meyyappan T, Chu HM, Knopf KB, Albala DM, Sant GR, Chander AC | display-authors = 6 | title = Live-cell phenotypic-biomarker microfluidic assay for the risk stratification of cancer patients via machine learning | journal = Nature Biomedical Engineering | volume = 2 | issue = 10 | pages = 761–772 | date = October 2018 | pmid = 30854249 | pmc = 6407716 | doi = 10.1038/s41551-018-0285-z }} [148] => [149] => Microfluidics is also suitable for [[Circulating tumor cell|circulating tumor cells (CTCs)]] and non-[[Circulating tumor cell|CTCs]] [[liquid biopsy]] analysis. Beads conjugate to anti‐[[Epithelial cell adhesion molecule|epithelial cell adhesion molecule (EpCAM)]] antibodies for [[Directional selection|positive selection]] in the [[Circulating tumor cell|CTCs]] [[Isolation chip|isolation chip (iCHIP)]].{{cite journal | vauthors = Karabacak NM, Spuhler PS, Fachin F, Lim EJ, Pai V, Ozkumur E, Martel JM, Kojic N, Smith K, Chen PI, Yang J, Hwang H, Morgan B, Trautwein J, Barber TA, Stott SL, Maheswaran S, Kapur R, Haber DA, Toner M | display-authors = 6 | title = Microfluidic, marker-free isolation of circulating tumor cells from blood samples | journal = Nature Protocols | volume = 9 | issue = 3 | pages = 694–710 | date = March 2014 | pmid = 24577360 | pmc = 4179254 | doi = 10.1038/nprot.2014.044 }} [[Circulating tumor cell|CTCs]] can also be detected by using the acidification of the [[tumor microenvironment]] and the difference in membrane capacitance.{{cite journal | vauthors = Warburg O, Wind F, Negelein E | title = The Metabolism of Tumors in the Body | journal = The Journal of General Physiology | volume = 8 | issue = 6 | pages = 519–530 | date = March 1927 | pmid = 19872213 | pmc = 2140820 | doi = 10.1085/jgp.8.6.519 }}{{cite journal | vauthors = Gascoyne PR, Noshari J, Anderson TJ, Becker FF | title = Isolation of rare cells from cell mixtures by dielectrophoresis | journal = Electrophoresis | volume = 30 | issue = 8 | pages = 1388–1398 | date = April 2009 | pmid = 19306266 | pmc = 3754902 | doi = 10.1002/elps.200800373 }} [[Circulating tumor cell|CTCs]] are isolated from blood by a microfluidic device, and are cultured [[Organ-on-a-chip|on-chip]], which can be a method to capture more biological information in a single analysis. For example, it can be used to test the cell survival rate of 40 different drugs or drug combinations.{{cite journal | vauthors = Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA | display-authors = 6 | title = Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility | journal = Science | volume = 345 | issue = 6193 | pages = 216–220 | date = July 2014 | pmid = 25013076 | pmc = 4358808 | doi = 10.1126/science.1253533 | bibcode = 2014Sci...345..216Y }} Tumor‐derived [[extracellular vesicle]]s can be isolated from urine and detected by an integrated double‐filtration microfluidic device; they also can be isolated from blood and detected by [[Digital pill|electrochemical sensing method]] with a two‐level amplification [[Enzyme assay|enzymatic assay]].{{cite journal | vauthors = Liang LG, Kong MQ, Zhou S, Sheng YF, Wang P, Yu T, Inci F, Kuo WP, Li LJ, Demirci U, Wang S | display-authors = 6 | title = An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer | journal = Scientific Reports | volume = 7 | issue = 1 | pages = 46224 | date = April 2017 | pmid = 28436447 | pmc = 5402302 | doi = 10.1038/srep46224 | bibcode = 2017NatSR...746224L }}{{cite journal | vauthors = Mathew DG, Beekman P, Lemay SG, Zuilhof H, Le Gac S, van der Wiel WG | title = Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes | journal = Nano Letters | volume = 20 | issue = 2 | pages = 820–828 | date = February 2020 | pmid = 31536360 | pmc = 7020140 | doi = 10.1021/acs.nanolett.9b02741 | bibcode = 2020NanoL..20..820M }} [150] => [151] => Tumor materials can directly be used for detection through microfluidic devices. To screen [[primary cell]]s for drugs, it is often necessary to distinguish cancerous cells from non-cancerous cells. A [[Lab-on-a-chip|microfluidic chip]] based on the capacity of cells to pass small constrictions can sort the cell types, [[Metastasis|metastases]].{{cite journal | vauthors = Liu Z, Lee Y, Jang JH, Li Y, Han X, Yokoi K, Ferrari M, Zhou L, Qin L | display-authors = 6 | title = Microfluidic cytometric analysis of cancer cell transportability and invasiveness | journal = Scientific Reports | volume = 5 | issue = 1 | pages = 14272 | date = September 2015 | pmid = 26404901 | pmc = 4585905 | doi = 10.1038/srep14272 | bibcode = 2015NatSR...514272L }} [[Droplet-based microfluidics|Droplet‐based microfluidic]] devices have the potential to screen different drugs or combinations of drugs, directly on the [[primary tumor]] sample with high accuracy. To improve this strategy, the microfluidic program with a sequential manner of drug cocktails, coupled with fluorescent barcodes, is more efficient.{{cite journal | vauthors = Eduati F, Utharala R, Madhavan D, Neumann UP, Longerich T, Cramer T, Saez-Rodriguez J, Merten CA | display-authors = 6 | title = A microfluidics platform for combinatorial drug screening on cancer biopsies | journal = Nature Communications | volume = 9 | issue = 1 | pages = 2434 | date = June 2018 | pmid = 29934552 | pmc = 6015045 | doi = 10.1038/s41467-018-04919-w | bibcode = 2018NatCo...9.2434E }} Another advanced strategy is detecting growth rates of single-cell by using suspended microchannel resonators, which can predict drug sensitivities of rare [[Circulating tumor cell|CTCs]].{{cite journal | vauthors = Stevens MM, Maire CL, Chou N, Murakami MA, Knoff DS, Kikuchi Y, Kimmerling RJ, Liu H, Haidar S, Calistri NL, Cermak N, Olcum S, Cordero NA, Idbaih A, Wen PY, Weinstock DM, Ligon KL, Manalis SR | display-authors = 6 | title = Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate | journal = Nature Biotechnology | volume = 34 | issue = 11 | pages = 1161–1167 | date = November 2016 | pmid = 27723727 | pmc = 5142231 | doi = 10.1038/nbt.3697 }} [152] => [153] => Microfluidics devices also can simulate the [[tumor microenvironment]], to help to test anticancer drugs. Microfluidic devices with 2D or [[3D cell culture]]s can be used to analyze spheroids for different cancer systems (such as [[lung cancer]] and [[ovarian cancer]]), and are essential for multiple anti-cancer drugs and toxicity tests. This strategy can be improved by increasing the throughput and production of spheroids. For example, one [[Droplet-based microfluidics|droplet-based microfluidic]] device for [[3D cell culture]] produces 500 spheroids per chip.{{cite journal | vauthors = Sart S, Tomasi RF, Amselem G, Baroud CN | title = Multiscale cytometry and regulation of 3D cell cultures on a chip | journal = Nature Communications | volume = 8 | issue = 1 | pages = 469 | date = September 2017 | pmid = 28883466 | pmc = 5589863 | doi = 10.1038/s41467-017-00475-x | bibcode = 2017NatCo...8..469S }} These spheroids can be cultured longer in different surroundings to analyze and monitor. The other advanced technology is [[Organ-on-a-chip|organs‐on‐a‐chip]], and it can be used to simulate several organs to determine the drug metabolism and activity based on [[Blood vessel|vessels]] mimicking, as well as mimic [[pH]], [[oxygen]]... to analyze the relationship between drugs and human organ surroundings. [154] => [155] => A recent strategy is single-cell [[ChIP sequencing|chromatin immunoprecipitation (ChiP)‐Sequencing]] in [[Droplet-based microfluidics|droplets]], which operates by combining droplet‐based single cell [[RNA-Seq|RNA sequencing]] with [[DNA barcoding|DNA‐barcoded]] antibodies, possibly to explore the [[Tumour heterogeneity|tumor heterogeneity]] by the [[genotype]] and [[phenotype]] to select the personalized anti-cancer drugs and prevent the cancer relapse.{{cite journal | vauthors = Grosselin K, Durand A, Marsolier J, Poitou A, Marangoni E, Nemati F, Dahmani A, Lameiras S, Reyal F, Frenoy O, Pousse Y, Reichen M, Woolfe A, Brenan C, Griffiths AD, Vallot C, Gérard A | display-authors = 6 | title = High-throughput single-cell ChIP-seq identifies heterogeneity of chromatin states in breast cancer | journal = Nature Genetics | volume = 51 | issue = 6 | pages = 1060–1066 | date = June 2019 | pmid = 31152164 | doi = 10.1038/s41588-019-0424-9 | s2cid = 171094979 }} [156] => [157] => == See also == [158] => {{Portal|Biology|Technology}} [159] => * [[Advanced Simulation Library]] [160] => * [[Droplet-based microfluidics]] [161] => * [[Fluidics]] [162] => * [[Induced-charge electrokinetics]] [163] => * [[Integrated fluidic circuit]] [164] => * [[Lab-on-a-chip]] [165] => * [[Microfluidic cell culture]] [166] => * [[Microfluidic modulation spectroscopy]] [167] => * [[Microphysiometry]] [168] => * [[Micropump]]s [169] => * [[Microvalve]]s [170] => * [[uFluids@Home]] [171] => * [[Paper-based microfluidics]] [172] => [173] => == References == [174] => {{reflist|30em}} [175] => [176] => == Further reading == [177] => [178] => ===Review papers=== [179] => {{refbegin}} [180] => * {{cite journal | vauthors = Yetisen AK, Akram MS, Lowe CR | title = Paper-based microfluidic point-of-care diagnostic devices | journal = Lab on a Chip | volume = 13 | issue = 12 | pages = 2210–2251 | date = June 2013 | pmid = 23652632 | doi = 10.1039/C3LC50169H | s2cid = 17745196 }} [181] => * {{cite journal | vauthors = Whitesides GM | title = The origins and the future of microfluidics | journal = Nature | volume = 442 | issue = 7101 | pages = 368–373 | date = July 2006 | pmid = 16871203 | doi = 10.1038/nature05058 | s2cid = 205210989 | bibcode = 2006Natur.442..368W }} [182] => * {{cite journal | vauthors = Seemann R, Brinkmann M, Pfohl T, Herminghaus S | title = Droplet based microfluidics | journal = Reports on Progress in Physics | volume = 75 | issue = 1 | pages = 016601 | date = January 2012 | pmid = 22790308 | doi = 10.1088/0034-4885/75/1/016601 | bibcode = 2012RPPh...75a6601S | s2cid = 5206697 }} [183] => * {{cite journal|vauthors = Squires TM, Quake SR|year = 2005|title = Microfluidics: Fluid physics at the nanoliter scale|journal = Reviews of Modern Physics|volume = 77|issue = 3|pages = 977–1026|bibcode = 2005RvMP...77..977S|doi = 10.1103/RevModPhys.77.977|url = http://authors.library.caltech.edu/1310/1/SQUrmp05.pdf }} [184] => * {{cite journal | vauthors = Yetisen AK, Volpatti LR | title = Patent protection and licensing in microfluidics | journal = Lab on a Chip | volume = 14 | issue = 13 | pages = 2217–2225 | date = July 2014 | pmid = 24825780 | doi = 10.1039/C4LC00399C | s2cid = 8669721 }} [185] => * {{cite journal|vauthors = Chen K|year = 2011|title = Microfluidics and the future of drug research|url = http://juls.library.utoronto.ca/index.php/juls/article/view/14551/12241|journal = Journal of Undergraduate Life Sciences|volume = 5|issue = 1|pages = 66–69|access-date = 2011-08-30|archive-url = https://web.archive.org/web/20120331110240/http://juls.library.utoronto.ca/index.php/juls/article/view/14551/12241|archive-date = 2012-03-31|url-status = dead }} [186] => * {{cite journal|vauthors = Angell JB, Terry SC, Barth PW|date=April 1983|title=Silicon Micromechanical Devices|journal=[[Scientific American]]|volume=248|issue=4|pages=44–55|bibcode = 1983SciAm.248d..44A|doi = 10.1038/scientificamerican0483-44 }} [187] => * {{cite journal | vauthors = Carugo D, Bottaro E, Owen J, Stride E, Nastruzzi C | title = Liposome production by microfluidics: potential and limiting factors | journal = Scientific Reports | volume = 6 | pages = 25876 | date = May 2016 | pmid = 27194474 | pmc = 4872163 | doi = 10.1038/srep25876 | bibcode = 2016NatSR...625876C }} [188] => * {{cite journal|vauthors = Chossat JB, Park YL, Wood RJ, Duchaine V|s2cid=14492585|date=September 2013|title=A Soft Strain Sensor Based on Ionic and Metal Liquids|journal=[[IEEE Sensors Journal]]|doi =10.1109/JSEN.2013.2263797|volume=13|issue=9|pages=3405–3414|bibcode=2013ISenJ..13.3405C|citeseerx=10.1.1.640.4976 }} [189] => * {{cite conference|vauthors = Tseng TM, Li M, Freitas DN, Mongersun A, Araci IE, Ho TY, Schlichtmann U|year =2018|title=Columba S: a scalable co-layout design automation tool for microfluidic large-scale integration|conference = Proceedings of the 55th Annual Design Automation Conference|pages=163|url=https://edawww.regent.e-technik.tu-muenchen.de/public/upload/201807122255_DAC18_ColumbaS_Tsun-Ming.pdf|archive-url=https://web.archive.org/web/20230409094736/https://edawww.regent.e-technik.tu-muenchen.de/public/upload/201807122255_DAC18_ColumbaS_Tsun-Ming.pdf|archive-date=April 9, 2023}} [190] => {{refend}} [191] => [192] => ===Books=== [193] => {{refbegin}} [194] => * {{cite book| vauthors = Bruus H |year = 2008|title = Theoretical Microfluidics|publisher = Oxford University Press|isbn = 978-0199235094 }} [195] => * Folch, Albert. ''Hidden in Plain Sight: The History, Science, and Engineering of Microfluidic Technology'' (MIT Press, 2022) [http://www.h-net.org/reviews/showrev.php?id=57939 online review] [196] => * {{cite book|vauthors = Herold KE, Rasooly A|year=2009|title=Lab-on-a-Chip Technology: Fabrication and Microfluidics|publisher=Caister Academic Press|isbn= 978-1-904455-46-2}} [197] => * {{cite book|title = Advances in Microfluidics|veditors = Kelly R|publisher = Pacific Northwest National Laboratory|location = Richland, Washington, USA|isbn = 978-953-510-106-2|date = 2012 }} [198] => * {{cite book|vauthors = Jenkins G, Mansfield CD|year = 2012|title = Microfluidic Diagnostics|publisher = Humana Press|isbn = 978-1-62703-133-2 }} [199] => * {{cite book|veditors = Li X, Zhou Y|year = 2013|title = Microfluidic devices for biomedical applications|publisher = Woodhead Publishing|isbn = 978-0-85709-697-5 }} [200] => * {{cite book|vauthors = Tabeling P|year = 2006|title = Introduction to Microfluidics|url = https://archive.org/details/introductiontomi0000tabe|url-access = registration|publisher = Oxford UP|isbn = 978-0-19-856864-3 }} [201] => [202] => {{refend}} [203] => {{Commons category|Microfluidics}} [204] => [205] => ===Education=== [206] => {{wikibooks|Microfluidics}} [207] => [208] => {{Scholia|topic}} [209] => {{Microtechnology}} [210] => {{Genomics}} [211] => [212] => [[Category:Microfluidics]] [213] => [[Category:Fluid dynamics]] [214] => [[Category:Nanotechnology]] [215] => [[Category:Biotechnology]] [216] => [[Category:Gas technologies]] [] => )
good wiki

Microfluidics

Microfluidics refers to a system that manipulates a small amount of fluids (10−9 to 10−18 liters) using small channels with sizes ten to hundreds micrometres. It is a multidisciplinary field that involves molecular analysis, molecular biology, and microelectronics.

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