Editing Microfluidics (section)

===Future directions===

==== Microfluidics for personalized cancer treatment ====
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.<ref name=":5">{{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 |bibcode=2020SeAcB.30327171H |s2cid=208705450}}</ref>

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.<ref>{{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 }}</ref> [[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]].<ref name=":5" /> 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.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref>

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)]].<ref>{{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 }}</ref> [[Circulating tumor cell|CTCs]] can also be detected by using the acidification of the [[tumor microenvironment]] and the difference in membrane capacitance.<ref>{{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 }}</ref><ref>{{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 }}</ref> [[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.<ref>{{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 }}</ref> 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]].<ref>{{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 }}</ref><ref>{{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 }}</ref>

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]].<ref>{{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 }}</ref> [[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.<ref>{{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 }}</ref> 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]].<ref>{{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 }}</ref>

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.<ref name=":6">{{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 }}</ref> 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.<ref name=":6" />

One strategy relevant to single-cell [[ChIP sequencing|chromatin immunoprecipitation (ChiP)‐Sequencing]] is [[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.<ref>{{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 }}</ref>