Skip to main content
SpringerLink
Log in

Microfluidics for Single-Cell Genomics

  • Chapter
  • First Online:
Microfluidics for Single-Cell Analysis

Part of the book series: Integrated Analytical Systems ((ANASYS))

  • 1139 Accesses

Abstract

Genomics is the systematic study of entire deoxyribonucleic acid (DNA) sequencing of an organism or virus. A single-cell DNA sequencing explores the heterogeneity among a cellular population of a biological sample and also predicts the growth and function of a living entity. However, efficient extraction of chromosomes from a single living cell requires sophisticated moods for sample preparation. Microfluidic devices offer several improvements including, effective heat transfer (enhanced the multiplication of DNA) and small volume (enabled the accurate quantification of DNA molecules) within the lysate of a single cell. However, at present, only one step such as single-cell isolation, cell lysis, or chromosome isolation from an individual cell and its amplification can be performed on-chip. Besides, microfluidics relies on external techniques for analysis of DNA. Therefore, the integration of multi-microfluidic systems is required for automated genome investigation. This chapter describes the advancement, limitations, and future prospects of microfluidic/nanofluidic for single-cell analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. International Human Genome Sequencing C, Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng J-F, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blöcker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen H-C, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JGR, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AFA, Stupka E, Szustakowki J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang S-P, Yeh R-F, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Raymond C, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Patrinos A, Morgan MJ (2001) Initial sequencing and analysis of the human genome. Nature 409:860. https://doi.org/10.1038/35057062

    Article  Google Scholar 

  2. Zhang J, Späth SS, Marjani SL, Zhang W, Pan X (2018) Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment. Prec Clin Med 1(1):29–48. https://doi.org/10.1093/pcmedi/pby007

    Article  Google Scholar 

  3. Gawad C, Koh W, Quake SR (2016) Single-cell genome sequencing: current state of the science. Nat Rev Genet 17:175. https://doi.org/10.1038/nrg.2015.16

    Article  CAS  PubMed  Google Scholar 

  4. Khan M, Mao S, Li W, Lin JM (2018) Microfluidic devices in the fast-growing domain of single-cell analysis. Chem Eur J 24(58):15398–15420. https://doi.org/10.1002/chem.201800305

    Article  CAS  PubMed  Google Scholar 

  5. Huang Q, Mao S, Khan M, Zhou L, Lin JM (2018) Dean flow assisted cell ordering system for lipid profiling in single-cells using mass spectrometry. Chem Comm 54(21):2595–2598. https://doi.org/10.1039/C7CC09608A

    Article  CAS  PubMed  Google Scholar 

  6. Huang Q, Mao S, Khan M, Lin JM (2019) Single-cell assay on microfluidic devices. Analyst 144(3):808–823. https://doi.org/10.1039/C8AN01079J

    Article  CAS  PubMed  Google Scholar 

  7. Khan M, Park S-Y (2014) General liquid-crystal droplets produced by microfluidics for urea detection. Sens Actuator B-Chem 202:516–522. https://doi.org/10.1016/j.snb.2014.05.115

    Article  CAS  Google Scholar 

  8. Ros A, Grief D (2008) In: Anselmetti D (ed) Single cell analysis technologies and applications. Wiley-VCH, pp 91–108

    Google Scholar 

  9. Wu J, Chen Q, Liu W, Lin J-M (2013) A simple and versatile microfluidic cell density gradient generator for quantum dot cytotoxicity assay. Lab Chip 13(10):1948–1954. https://doi.org/10.1039/C3LC00041A

    Article  CAS  PubMed  Google Scholar 

  10. Sung WC, Makamba H, Chen SH (2005) Chip-based microfluidic devices coupled with electrospray ionization-mass spectrometry. Electrophoresis 26(9):1783–1791. https://doi.org/10.1002/elps.200410346

    Article  CAS  PubMed  Google Scholar 

  11. Gijs MAM, Lacharme F, Lehmann U (2010) Microfluidic applications of magnetic particles for biological analysis and catalysis. Chem Rev 110(3):1518–1563. https://doi.org/10.1021/cr9001929

    Article  CAS  PubMed  Google Scholar 

  12. Jiang H, Weng X, Li D (2011) Microfluidic whole-blood immunoassays. Microfluid Nanofluid 10(5):941–964. https://doi.org/10.1007/s10404-010-0718-9

    Article  CAS  Google Scholar 

  13. Jeon S, Kim US, Jeon W, Shin CB, Hong S, Choi I, Lee S, Yi J (2009) Fabrication of multicomponent protein microarrays with microfluidic devices of poly(dimethylsiloxane). Macromol Res 17(3):192–196. https://doi.org/10.1007/bf03218678

    Article  CAS  Google Scholar 

  14. Choi C-H, Jung J-H, Hwang T-S, Lee C-S (2009) In situ microfluidic synthesis of monodisperse PEG microspheres. Macromol Res 17(3):163–167. https://doi.org/10.1007/bf03218673

    Article  CAS  Google Scholar 

  15. He X, Chen Q, Zhang Y, Lin JM (2014) Recent advances in microchip-mass spectrometry for biological analysis. TrAC-Trends Anal Chem 53:84–97. https://doi.org/10.1016/j.trac.2013.09.013

    Article  CAS  Google Scholar 

  16. Jie M, Mao S, Li H, Lin JM (2017) Multi-channel microfluidic chip-mass spectrometry platform for cell analysis. Chin Chem Lett 28(8):1625–1630. https://doi.org/10.1016/j.cclet.2017.05.024

    Article  CAS  Google Scholar 

  17. Mao S, Zhang J, Li H, Lin JM (2013) Strategy for signaling molecule detection by using an integrated microfluidic device coupled with mass spectrometry to study cell-to-cell communication. Anal Chem 85(2):868–876. https://doi.org/10.1021/ac303164b

    Article  CAS  PubMed  Google Scholar 

  18. Lin L, Lin X, Lin L, Feng Q, Kitamori T, Lin JM, Sun J (2017) Integrated microfluidic platform with multiple functions to probe tumor–endothelial cell interaction. Anal Chem 89(18):10037–10044. https://doi.org/10.1021/acs.analchem.7b02593

    Article  CAS  PubMed  Google Scholar 

  19. Liu W, Lin JM (2016) Online monitoring of lactate efflux by multi-channel microfluidic chip-mass spectrometry for rapid drug evaluation. ACS Sens 1(4):344–347. https://doi.org/10.1021/acssensors.5b00221

    Article  CAS  Google Scholar 

  20. Gao D, Liu H, Lin JM, Wang Y, Jiang Y (2013) Characterization of drug permeability in Caco-2 monolayers by mass spectrometry on a membrane-based microfluidic device. Lab Chip 13(5):978–985. https://doi.org/10.1039/C2LC41215B

    Article  CAS  PubMed  Google Scholar 

  21. Grün D, van Oudenaarden A (2015) Design and analysis of single-cell sequencing experiments. Cell 163(4):799–810. https://doi.org/10.1016/j.cell.2015.10.039

    Article  CAS  PubMed  Google Scholar 

  22. Livesey FJ (2003) Strategies for microarray analysis of limiting amounts of RNA. Brief Func Genomics Proteomics 2(1):31–36

    Article  CAS  Google Scholar 

  23. Hosic S, Murthy SK, Koppes AN (2016) Microfluidic sample preparation for single cell analysis. Anal Chem 88(1):354–380. https://doi.org/10.1021/acs.analchem.5b04077

    Article  CAS  PubMed  Google Scholar 

  24. Cheung VG, Nelson SF (1996) Whole genome amplification using a degenerate oligonucleotide primer allows hundreds of genotypes to be performed on less than one nanogram of genomic DNA. Proc Natl Acad Sci 93(25):14676–14679. https://doi.org/10.1073/pnas.93.25.14676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kopp MU, Mello AJd, Manz A (1998) Chemical amplification: continuous-flow PCR on a chip. Science 280:1046–1048. https://doi.org/10.1126/science.280.5366.1046

    Article  CAS  PubMed  Google Scholar 

  26. Zhang W, Li N, Koga D, Zhang Y, Zeng H, Nakajima H, Lin JM, Uchiyama K (2018) Inkjet printing based droplet generation for integrated online digital polymerase chain reaction. Anal Chem 90:5329–5334. https://doi.org/10.1021/acs.analchem.8b00463

    Article  CAS  PubMed  Google Scholar 

  27. Ahrberg CD, Manz A, Chung BG (2016) Polymerase chain reaction in microfluidic devices. Lab Chip 16(20):3866–3884. https://doi.org/10.1039/C6LC00984K

    Article  CAS  PubMed  Google Scholar 

  28. Leung K, Klaus A, Lin BK, Laks E, Biele J, Lai D, Bashashati A, Huang Y-F, Aniba R, Moksa M, Steif A, Mes-Masson A-M, Hirst M, Shah SP, Aparicio S, Hansen CL (2016) Robust high-performance nanoliter-volume single-cell multiple displacement amplification on planar substrates. Proc Natl Acad Sci 113(30):8484–8489. https://doi.org/10.1073/pnas.1520964113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang J, Fan HC, Behr B, Quake SR (2012) Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150(2):402–412. https://doi.org/10.1016/j.cell.2012.06.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Marcus JS, Anderson WF, Quake SR (2006) Parallel picoliter RT-PCR assays using microfluidics. Anal Chem 78(3):956–958. https://doi.org/10.1021/ac0513865

    Article  CAS  PubMed  Google Scholar 

  31. White AK, VanInsberghe M, Petriv OI, Hamidi M, Sikorski D, Marra MA, Piret J, Aparicio S, Hansen CL (2011) High-throughput microfluidic single-cell RT-qPCR. Proc Natl Acad Sci 108(34):13999–14004. https://doi.org/10.1073/pnas.1019446108

    Article  PubMed  PubMed Central  Google Scholar 

  32. Marcy Y, Ishoey T, Lasken RS, Stockwell TB, Walenz BP, Halpern AL, Beeson KY, Goldberg SMD, Quake SR (2007) Nanoliter reactors improve multiple displacement amplification of genomes from single cells. PLoS Genet 3(9):e155. https://doi.org/10.1371/journal.pgen.0030155

    Article  CAS  PubMed Central  Google Scholar 

  33. Yu Z, Lu S, Huang Y (2014) Microfluidic whole genome amplification device for single cell sequencing. Anal Chem 86(19):9386–9390. https://doi.org/10.1021/ac5032176

    Article  CAS  PubMed  Google Scholar 

  34. Meyer LR, Zweig AS, Hinrichs AS, Karolchik D, Kuhn RM, Wong M, Sloan CA, Rosenbloom KR, Roe G, Rhead B, Raney BJ, Pohl A, Malladi VS, Li CH, Lee BT, Learned K, Kirkup V, Hsu F, Heitner S, Harte RA, Haeussler M, Guruvadoo L, Goldman M, Giardine BM, Fujita PA, Dreszer TR, Diekhans M, Cline MS, Clawson H, Barber GP, Haussler D, Kent WJ (2013) The UCSC genome browser database: extensions and updates 2013. Nucl Acids Res 41(D1):D64–D69. https://doi.org/10.1093/nar/gks1048

    Article  CAS  PubMed  Google Scholar 

  35. Cunningham F, Amode MR, Barrell D, Beal K, Billis K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fitzgerald S, Gil L, Girón CG, Gordon L, Hourlier T, Hunt SE, Janacek SH, Johnson N, Juettemann T, Kähäri AK, Keenan S, Martin FJ, Maurel T, McLaren W, Murphy DN, Nag R, Overduin B, Parker A, Patricio M, Perry E, Pignatelli M, Riat HS, Sheppard D, Taylor K, Thormann A, Vullo A, Wilder SP, Zadissa A, Aken BL, Birney E, Harrow J, Kinsella R, Muffato M, Ruffier M, Searle SMJ, Spudich G, Trevanion SJ, Yates A, Zerbino DR, Flicek P (2015) Ensembl 2015. Nucl Acids Res 43(D1):D662–D669. https://doi.org/10.1093/nar/gku1010

    Article  CAS  PubMed  Google Scholar 

  36. Venkatraman ES, Olshen AB (2007) A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics 23(6):657–663. https://doi.org/10.1093/bioinformatics/btl646

    Article  CAS  PubMed  Google Scholar 

  37. Seiser EL, Innocenti F (2015) Hidden markov model-based CNV detection algorithms for illumina genotyping microarrays. Cancer inform 13(Suppl 7):77–83. https://doi.org/10.4137/CIN.S16345

    Article  PubMed  PubMed Central  Google Scholar 

  38. Nielsen R, Paul JS, Albrechtsen A, Song YS (2011) Genotype and SNP calling from next-generation sequencing data. Nat Rev Genet 12:443. https://doi.org/10.1038/nrg2986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Voet T, Kumar P, Van Loo P, Cooke SL, Marshall J, Lin M-L, Zamani Esteki M, Van der Aa N, Mateiu L, McBride DJ, Bignell GR, McLaren S, Teague J, Butler A, Raine K, Stebbings LA, Quail MA, D’Hooghe T, Moreau Y, Futreal PA, Stratton MR, Vermeesch JR, Campbell PJ (2013) Single-cell paired-end genome sequencing reveals structural variation per cell cycle. Nucl Acids Res 41(12):6119–6138. https://doi.org/10.1093/nar/gkt345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Baslan T, Kendall J, Rodgers L, Cox H, Riggs M, Stepansky A, Troge J, Ravi K, Esposito D, Lakshmi B, Wigler M, Navin N, Hicks J (2012) Genome-wide copy number analysis of single cells. Nat Protoc 7:1024. https://doi.org/10.1038/nprot.2012.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Zong C, Lu S, Chapman AR, Xie XS (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338(6114):1622–1626. https://doi.org/10.1126/science.1229164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fan HC, Wang J, Potanina A, Quake SR (2010) Whole-genome molecular haplotyping of single cells. Nat Biotech 29:51. https://doi.org/10.1038/nbt.1739

    Article  CAS  Google Scholar 

  43. Szulwach KE, Chen P, Wang X, Wang J, Weaver LS, Gonzales ML, Sun G, Unger MA, Ramakrishnan R (2015) Single-cell genetic analysis using automated microfluidics to resolve somatic mosaicism. PLoS ONE 10(8):e0135007–e0135007. https://doi.org/10.1371/journal.pone.0135007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Islam S, Zeisel A, Joost S, La Manno G, Zajac P, Kasper M, Lönnerberg P, Linnarsson S (2013) Quantitative single-cell RNA-seq with unique molecular identifiers. Nat Meth 11:163. https://doi.org/10.1038/nmeth.2772

    Article  CAS  Google Scholar 

  45. Pollen AA, Nowakowski TJ, Shuga J, Wang X, Leyrat AA, Lui JH, Li N, Szpankowski L, Fowler B, Chen P, Ramalingam N, Sun G, Thu M, Norris M, Lebofsky R, Toppani D, Kemp DW II, Wong M, Clerkson B, Jones BN, Wu S, Knutsson L, Alvarado B, Wang J, Weaver LS, May AP, Jones RC, Unger MA, Kriegstein AR, West JAA (2014) Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat Biotechnol 32:1053. https://doi.org/10.1038/nbt.2967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Goldstein LD, Chen Y-JJ, Dunne J, Mir A, Hubschle H, Guillory J, Yuan W, Zhang J, Stinson J, Jaiswal B, Pahuja KB, Mann I, Schaal T, Chan L, Anandakrishnan S, Lin C-W, Espinoza P, Husain S, Shapiro H, Swaminathan K, Wei S, Srinivasan M, Seshagiri S, Modrusan Z (2017) Massively parallel nanowell-based single-cell gene expression profiling. BMC Genom 18(1):519. https://doi.org/10.1186/s12864-017-3893-1

    Article  CAS  Google Scholar 

  47. Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, Francis JM, Zhang C-Z, Shalek AK, Satija R, Trombetta JJ, Lu D, Tallapragada N, Tahirova N, Kim S, Blumenstiel B, Sougnez C, Lowe A, Wong B, Auclair D, Van Allen EM, Nakabayashi M, Lis RT, Lee G-SM, Li T, Chabot MS, Ly A, Taplin M-E, Clancy TE, Loda M, Regev A, Meyerson M, Hahn WC, Kantoff PW, Golub TR, Getz G, Boehm JS, Love JC (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32:479. https://doi.org/10.1038/nbt.2892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gole J, Gore A, Richards A, Chiu Y-J, Fung H-L, Bushman D, Chiang H-I, Chun J, Lo Y-H, Zhang K (2013) Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells. Nat Biotechnol 31(12):1126–1132. https://doi.org/10.1038/nbt.2720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. He M, Edgar JS, Jeffries GD, Lorenz RM, Shelby JP, Chiu DT (2005) Selective encapsulation of single cells and subcellular organelles into picoliter- and femtoliter-volume droplets. Anal Chem 77(6):1539–1544. https://doi.org/10.1021/ac0480850

    Article  CAS  PubMed  Google Scholar 

  50. Lim SW, Tran TM, Abate AR (2015) PCR-activated cell sorting for cultivation-free enrichment and sequencing of rare microbes. PLoS ONE 10(1):e0113549. https://doi.org/10.1371/journal.pone.0113549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kiss MM, Ortoleva-Donnelly L, Beer NR, Warner J, Bailey CG, Colston BW, Rothberg JM, Link DR, Leamon JH (2008) High-throughput quantitative polymerase chain reaction in picoliter droplets. Anal Chem 80(23):8975–8981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Utada AS, Lorenceau E, Link DR, Kaplan PD, Stone HA, Weitz DA (2005) Monodisperse double emulsions generated from a microcapillary device. Science 308(5721):537–541. https://doi.org/10.1126/science.1109164

    Article  CAS  PubMed  Google Scholar 

  53. Kumaresan P, Yang CJ, Cronier SA, Blazej RG, Mathies RA (2008) High-throughput single copy DNA amplification and cell analysis in engineered nanoliter droplets. Anal Chem 80(10):3522–3529. https://doi.org/10.1021/ac800327d

    Article  CAS  PubMed  Google Scholar 

  54. Fu Y, Li C, Lu S, Zhou W, Tang F, Xie XS, Huang Y (2015) Uniform and accurate single-cell sequencing based on emulsion whole-genome amplification. Proc Natl Acad Sci USA 112(38):11923–11928. https://doi.org/10.1073/pnas.1513988112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pellegrino M, Sciambi A, Treusch S, Durruthy-Durruthy R, Gokhale K, Jacob J, Chen TX, Geis JA, Oldham W, Matthews J, Kantarjian H, Futreal PA, Patel K, Jones KW, Takahashi K, Eastburn DJ (2018) High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics. Genome Res 28(9):1345–1352. https://doi.org/10.1101/gr.232272.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Khilko Y, Weyman PD, Glass JI, Adams MD, McNeil MA, Griffin PB (2018) DNA assembly with error correction on a droplet digital microfluidics platform. BMC Biotechnol 18(1):37. https://doi.org/10.1186/s12896-018-0439-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhu Z, Yang CJ (2017) Hydrogel droplet microfluidics for high-throughput single molecule/cell analysis. Acc Chem Res 50(1):22–31. https://doi.org/10.1021/acs.accounts.6b00370

    Article  CAS  PubMed  Google Scholar 

  58. Novak R, Zeng Y, Shuga J, Venugopalan G, Fletcher DA, Smith MT, Mathies RA (2011) Single-cell multiplex gene detection and sequencing with microfluidically generated agarose emulsions. Angew Chem Intl Ed 50(2):390–395. https://doi.org/10.1002/anie.201006089

    Article  CAS  Google Scholar 

  59. Bigdeli S, Dettloff RO, Frank CW, Davis RW, Crosby LD (2015) A simple method for encapsulating single cells in alginate microspheres allows for direct PCR and whole genome amplification. PLoS ONE 10(2):e0117738. https://doi.org/10.1371/journal.pone.0117738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zheng GXY, Lau BT, Schnall-Levin M, Jarosz M, Bell JM, Hindson CM, Kyriazopoulou-Panagiotopoulou S, Masquelier DA, Merrill L, Terry JM, Mudivarti PA, Wyatt PW, Bharadwaj R, Makarewicz AJ, Li Y, Belgrader P, Price AD, Lowe AJ, Marks P, Vurens GM, Hardenbol P, Montesclaros L, Luo M, Greenfield L, Wong A, Birch DE, Short SW, Bjornson KP, Patel P, Hopmans ES, Wood C, Kaur S, Lockwood GK, Stafford D, Delaney JP, Wu I, Ordonez HS, Grimes SM, Greer S, Lee JY, Belhocine K, Giorda KM, Heaton WH, McDermott GP, Bent ZW, Meschi F, Kondov NO, Wilson R, Bernate JA, Gauby S, Kindwall A, Bermejo C, Fehr AN, Chan A, Saxonov S, Ness KD, Hindson BJ, Ji HP (2016) Haplotyping germline and cancer genomes with high-throughput linked-read sequencing. Nat Biotechnol 34:303. https://doi.org/10.1038/nbt.3432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Macaulay IC, Ponting CP, Voet T (2017) Single-cell multiomics: multiple measurements from single cells. Trends Genet 33(2):155–168. https://doi.org/10.1016/j.tig.2016.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Aguilar CA, Craighead HG (2013) Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics. Nat Nanotechnol 8(10):709–718. https://doi.org/10.1038/nnano.2013.195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lagally ET, Medintz I, Mathies RA (2001) Single-molecule DNA amplification and analysis in an integrated microfluidic device. Anal Chem 73(3):565–570. https://doi.org/10.1021/ac001026b

    Article  CAS  PubMed  Google Scholar 

  64. Le Roux D, Root BE, Reedy CR, Hickey JA, Scott ON, Bienvenue JM, Landers JP, Chassagne L, de Mazancourt P (2014) DNA analysis using an integrated microchip for multiplex PCR amplification and electrophoresis for reference samples. Anal Chem 86(16):8192–8199. https://doi.org/10.1021/ac501666b

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China

    Mashooq Khan & Jin-Ming Lin

Authors
  1. Mashooq Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Ming Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jin-Ming Lin .

Editor information

Editors and Affiliations

  1. Department of Chemistry, Tsinghua University, Beijing, China

    Jin-Ming Lin

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khan, M., Lin, JM. (2019). Microfluidics for Single-Cell Genomics. In: Lin, JM. (eds) Microfluidics for Single-Cell Analysis. Integrated Analytical Systems. Springer, Singapore. https://doi.org/10.1007/978-981-32-9729-6_6

Download citation

Publish with us

Policies and ethics

Search

Navigation