Skip to main content

Droplet-Based Microfluidics for Single-Cell Encapsulation and Analysis

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

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

Abstract

Droplet microfluidic techniques have been rapidly developed as a powerful tool to perform high-throughput and low-cost analysis of single cells. Microscale droplets can be easily produced by a microfluidic manipulation to encapsulate and manipulate single cells for precise analysis. This offers a new approach to measure genetic and functional heterogeneity of cell division, growth, metabolism, and apoptosis. Functional characteristics of cellular molecules, such as DNA , RNA, and proteins, can be realized at a single-cell level. In this chapter, we will present a general introduction to single-cell analysis involving droplet-based microfluidic techniques. We will highlight the current state of droplet-based microfluidic single-cell analysis for deep insights understanding the biological process at the single-cell level.

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

Access this chapter

eBook
USD 16.99
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. Maxmen A (2011) Single-cell analysis: Imaging is everything. Nature 480(7375):139–141. https://doi.org/10.1038/nj7375-139a

    Article  CAS  PubMed  Google Scholar 

  2. Reece A, Xia B, Jiang Z, Noren B, McBride R, Oakey J (2016) Microfluidic techniques for high throughput single cell analysis. Curr Opin Biotechnol 40:90–96. https://doi.org/10.1016/j.copbio.2016.02.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wu J, Li H, Chen Q, Lin X, Liu W, Lin JM (2014) Statistical single-cell analysis of cell cycle-dependent quantum dot cytotoxicity and cellular uptake using a microfluidic system. RSC Adv 4:24929–24934. https://doi.org/10.1039/C4RA01665C

    Article  CAS  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  Google Scholar 

  5. Zhang Q, Mao S, Khan M, Feng S, Zhang W, Li W et al (2018) In situ partial treatment of single cells by laminar flow in the “open space”. Anal Chem 91:1644–1650. https://doi.org/10.1021/acs.analchem.8b05313

    Article  CAS  PubMed  Google Scholar 

  6. Mao S, Zhang Q, Liu W, Huang Q, Khan M, Zhang W et al (2019) Chemical operations on a living single cell by open microfluidics for wound repair studies and organelle transport analysis. Chem Sci 10:2081–2087. https://doi.org/10.1039/C8SC05104F

    Article  CAS  PubMed  Google Scholar 

  7. Chen Q, He Z, Liu W, Lin X, Wu J, Li H et al (2015) Engineering cell-compatible paper chips for cell culturing, drug screening, and mass spectrometric sensing. Adv Healthc Mater 4(15):2291–2296. https://doi.org/10.1002/adhm.20150038

    Article  CAS  PubMed  Google Scholar 

  8. Chen Q, Lin JM (2018) Microfluidic cell isolation and recognition for biomedical applications. In: Cell analysis on microfluidics. Springer, pp 95–118. https://doi.org/10.1007/978-981-10-5394-8_3

    Google Scholar 

  9. Chen Q, Wu J, Zhang Y, Lin JM (2012) Qualitative and quantitative analysis of tumor cell metabolism via stable isotope labeling assisted microfluidic chip electrospray ionization mass spectrometry. Anal Chem 84(3):1695–1701. https://doi.org/10.1021/ac300003k

    Article  CAS  PubMed  Google Scholar 

  10. Chen Q, Wu J, Zhuang Q, Lin X, Zhang J, Lin JM (2013) Microfluidic isolation of highly pure embryonic stem cells using feeder-separated co-culture system. Sci Rep 3:2433. https://doi.org/10.1038/srep02433

    Article  PubMed  PubMed Central  Google Scholar 

  11. El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442:403–411. https://doi.org/10.1038/nature05063

    Article  CAS  PubMed  Google Scholar 

  12. Yu L, Ng SR, Xu Y, Dong H, Wang YJ, Li CM (2013) Advances of lab-on-a-chip in isolation, detection and post-processing of circulating tumour cells. Lab Chip 13:3163–3182. https://doi.org/10.1039/C3LC00052D

    Article  CAS  PubMed  Google Scholar 

  13. Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH et al (2013) Microfluidic device for single-cell analysis. Anal Chem 75:3581–3586. https://doi.org/10.1021/ac0340758

    Article  CAS  Google Scholar 

  14. Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507:181–189. https://doi.org/10.1038/nature13118

    Article  CAS  PubMed  Google Scholar 

  15. Wu J, Chen Q, Lin JM (2016) Biochemical analysis on microfluidic chips. Trends Anal Chem 80:213–231. https://doi.org/10.1016/j.trac.2016.03.013

    Article  CAS  Google Scholar 

  16. Chen Q, Wu J, Zhang Y, Lin Z, Lin JM (2012) Targeted isolation and analysis of single tumor cells with aptamer-encoded microwell array on microfluidic device. Lab Chip 12:5180–5185. https://doi.org/10.1039/C2LC40858A

    Article  CAS  PubMed  Google Scholar 

  17. Mao S, Zhang W, Huang Q, Khan M, Li H, Uchiyama K et al (2018) In situ scatheless cell detachment reveals correlation between adhesion strength and viability at single-cell resolution. Angew Chem Int Ed 57:236–240. https://doi.org/10.1002/anie.201710273

    Article  CAS  Google Scholar 

  18. Teh SY, Lin R, Hung LH, Lee AP (2008) Droplet microfluidics. Lab Chip 8:198–220. https://doi.org/10.1039/B715524G

    Article  CAS  PubMed  Google Scholar 

  19. Casadevall i Solvas X, deMello A (2011) Droplet microfluidics: recent developments and future applications. Chem Commun 47:1936–1942. https://doi.org/10.1039/c0cc02474k

    Article  CAS  Google Scholar 

  20. Shang L, Cheng Y, Zhao Y (2017) Emerging droplet microfluidics. Chem Rev 117:7964–8040. https://doi.org/10.1021/acs.chemrev.6b00848

    Article  CAS  PubMed  Google Scholar 

  21. Baret JC (2012) Surfactants in droplet-based microfluidics. Lab Chip 12:422–433. https://doi.org/10.1039/C1LC20582J

    Article  CAS  PubMed  Google Scholar 

  22. Yin H, Marshall D (2012) Microfluidics for single cell analysis. Curr Opin Biotechnol 23:110–119. https://doi.org/10.1016/j.copbio.2011.11.002

    Article  CAS  PubMed  Google Scholar 

  23. Huebner A, Srisa-Art M, Holt D, Abell C, Hollfelder F, deMello AJ et al (2007) Quantitative detection of protein expression in single cells using droplet microfluidics. Chem Commun 1218–1220. https://doi.org/10.1039/b618570c

  24. Zhu Z, Zhang W, Leng X, Zhang M, Guan Z, Lu J et al (2012) Highly sensitive and quantitative detection of rare pathogens through agarose droplet microfluidic emulsion PCR at the single-cell level. Lab Chip 12:3907–3913. https://doi.org/10.1039/C2LC40461C

    Article  CAS  PubMed  Google Scholar 

  25. Leng X, Zhang W, Wang C, Cui L, Yang CJ (2010) Agarose droplet microfluidics for highly parallel and efficient single molecule emulsion PCR. Lab Chip 10:2841–2843. https://doi.org/10.1039/C0LC00145G

    Article  CAS  PubMed  Google Scholar 

  26. Zeng Y, Novak R, Shuga J, Smith MT, Mathies RA (2010) High-performance single cell genetic analysis using microfluidic emulsion generator arrays. Anal Chem 82:3183–3190. https://doi.org/10.1021/ac902683t

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chen Q, Chen D, Wu J, Lin JM (2016) Flexible control of cellular encapsulation, permeability, and release in a droplet-templated bifunctional copolymer scaffold. Biomicrofluidics 10:064115. https://doi.org/10.1063/1.4972107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang N, Mao S, Liu W, Wu J, Li H, Lin JM (2014) Online monodisperse droplets based liquid–liquid extraction on a continuously flowing system by using microfluidic devices. RSC Adv 4:11919–11926. https://doi.org/10.1039/C4RA00984C

    Article  CAS  Google Scholar 

  29. Tanaka H, Yamamoto S, Nakamura A, Nakashoji Y, Okura N, Nakamoto N et al (2015) Hands-off preparation of monodisperse emulsion droplets using a poly(dimethylsiloxane) microfluidic chip for droplet digital PCR. Anal Chem 87:4134–4143. https://doi.org/10.1021/ac503169h

    Article  CAS  PubMed  Google Scholar 

  30. Nabavi SA, Vladisavljević GT, Gu S, Ekanem EE (2015) Double emulsion production in glass capillary microfluidic device: parametric investigation of droplet generation behaviour. Chem Eng Sci 130:183–196. https://doi.org/10.1016/j.ces.2015.03.004

    Article  CAS  Google Scholar 

  31. Chen Q, Utech S, Chen D, Prodanovic R, Lin JM, Weitz DA (2016) Controlled assembly of heterotypic cells in a core-shell scaffold: organ in a droplet. Lab Chip 16:1346–1349. https://doi.org/10.1039/C6LC00231E

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xia Y, Whitesides GM (1998) Soft Lithography. Angew Chem Int Ed 37:550–575. https://doi.org/10.1002/(SICI)1521-3773(19980316)37:5%3c550:AID-ANIE550%3e3.0.CO;2-G

    Article  CAS  Google Scholar 

  33. Toepke MW, Beebe DJ (2006) PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6:1484–1486. https://doi.org/10.1039/B612140C

    Article  CAS  PubMed  Google Scholar 

  34. Beer NR, Wheeler EK, Lee-Houghton L, Watkins N, Nasarabadi S, Hebert N et al (2008) On-chip single-copy real-time reverse-transcription PCR in isolated picoliter droplets. Anal Chem 80:1854–1858. https://doi.org/10.1021/ac800048k

    Article  CAS  PubMed  Google Scholar 

  35. Joensson HN, Andersson Svahn H (2012) Droplet microfluidics—a tool for single-cell analysis. Angew Chem Int Ed 51:12176–12192. https://doi.org/10.1002/anie.201200460

    Article  CAS  Google Scholar 

  36. Gu H, Duits MH, Mugele F (2011) Droplets formation and merging in two-phase flow microfluidics. Int J Mol Sci 12:2572–2597. https://doi.org/10.3390/ijms12042572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Collins DJ, Neild A, deMello A, Liu AQ, Ai Y (2015) The Poisson distribution and beyond: methods for microfluidic droplet production and single cell encapsulation. Lab Chip 15:3439–3459. https://doi.org/10.1039/C5LC00614G

    Article  CAS  PubMed  Google Scholar 

  38. Chen D, Amstad E, Zhao C-X, Cai L, Fan J, Chen Q et al (2017) Biocompatible amphiphilic hydrogel-solid dimer particles as colloidal surfactants. ACS Nano 11:11978–11985. https://doi.org/10.1021/acsnano.7b03110

    Article  CAS  PubMed  Google Scholar 

  39. Zhang Y, Li H, Ma Y, Lin JM (2014) Paper spray mass spectrometry-based method for analysis of droplets in a gravity-driven microfluidic chip. Analyst 139:1023–1029. https://doi.org/10.1039/C3AN01769A

    Article  CAS  PubMed  Google Scholar 

  40. Liu J, Lin JM, Knopp D (2008) Using a circular groove surrounded inlet to generate monodisperse droplets inside a microfluidic chip in a gravity-driven manner. J Micromech Microeng 18:095014. https://doi.org/10.1088/0960-1317/18/9/095014

    Article  CAS  Google Scholar 

  41. Liu W, Mao S, Wu J, Lin JM (2013) Development and applications of paper-based electrospray ionization-mass spectrometry for monitoring of sequentially generated droplets. Analyst 138:2163–2170. https://doi.org/10.1039/C3AN36404F

    Article  CAS  PubMed  Google Scholar 

  42. Chen F, Lin L, Zhang J, He Z, Uchiyama K, Lin JM (2016) Single-cell analysis using drop-on-demand inkjet printing and probe electrospray ionization mass spectrometry. Anal Chem 88:4354–4360. https://doi.org/10.1021/acs.analchem.5b04749

    Article  CAS  PubMed  Google Scholar 

  43. Shembekar N, Chaipan C, Utharala R, Merten CA (2016) Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. Lab Chip 16:1314–1331. https://doi.org/10.1039/C6LC00249H

    Article  CAS  PubMed  Google Scholar 

  44. Clausell-Tormos J, Lieber D, Baret J-C, El-Harrak A, Miller OJ, Frenz L et al (2008) Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms. Chem Biol 15:427–437. https://doi.org/10.1016/j.chembiol.2008.04.004

    Article  CAS  PubMed  Google Scholar 

  45. Kemna EW, Schoeman RM, Wolbers F, Vermes I, Weitz DA, Van Den Berg A (2012) High-yield cell ordering and deterministic cell-in-droplet encapsulation using Dean flow in a curved microchannel. Lab Chip 12:2881–2887. https://doi.org/10.1039/C2LC00013J

    Article  CAS  PubMed  Google Scholar 

  46. Li W, Zhang L, Ge X, Xu B, Zhang W, Qu L et al (2018) Microfluidic fabrication of microparticles for biomedical applications. Chem Soc Rev 47:5646–5683. https://doi.org/10.1039/C7CS00263G

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lima AC, Sher P, Mano JF (2012) Production methodologies of polymeric and hydrogel particles for drug delivery applications. Expert Opin Drug Deliv 9:231–248. https://doi.org/10.1517/17425247.2012.652614

    Article  CAS  PubMed  Google Scholar 

  48. Mao AS, Shin J-W, Utech S, Wang H, Uzun O, Li W et al (2017) Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery. Nat Mater 16:236–243. https://doi.org/10.1038/nmat4781

    Article  CAS  PubMed  Google Scholar 

  49. Kamperman T, Karperien M, Le Gac S, Leijten J (2018) Single-cell microgels: technology, challenges, and applications. Trends Biotechnol 2018(36):850–865. https://doi.org/10.1016/j.tibtech.2018.03.001

    Article  CAS  Google Scholar 

  50. Tumarkin E, Kumacheva E (2009) Microfluidic generation of microgels from synthetic and natural polymers. Chem Soc Rev 38:2161–2168. https://doi.org/10.1039/B809915B

    Article  CAS  PubMed  Google Scholar 

  51. Wan J (2012) Microfluidic-based synthesis of hydrogel particles for cell microencapsulation and cell-based drug delivery. Polymers 4:1084–1108. https://doi.org/10.3390/polym4021084

    Article  CAS  Google Scholar 

  52. Zhu Z, Yang CJ (2016) Hydrogel droplet microfluidics for high-throughput single molecule/cell analysis. Acc Chem Res 50:22–31. https://doi.org/10.1021/acs.accounts.6b00370

    Article  CAS  PubMed  Google Scholar 

  53. Rinaudo M (2008) Main properties and current applications of some polysaccharides as biomaterials. Polym Int 57:397–430. https://doi.org/10.1002/pi.2378

    Article  CAS  Google Scholar 

  54. Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37:106–126. https://doi.org/10.1016/j.progpolymsci.2011.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Williams BR, Gelman RA, Poppke DC, Piez KA (1978) Collagen fibril formation. Optimal in vitro conditions and preliminary kinetic results. J Biol Chem 253:6578–6585

    CAS  PubMed  Google Scholar 

  56. Wu J, Xie L, Lin WZY, Chen Q (2017) Biomimetic nanofibrous scaffolds for neural tissue engineering and drug development. Drug Discov Today 22:1375–1384. https://doi.org/10.1016/j.drudis.2017.03.007

    Article  CAS  PubMed  Google Scholar 

  57. Hern DL, Hubbell JA (1998) Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing. J Biomed Mater Res 39:266–276. https://doi.org/10.1002/(SICI)1097-4636(199802)39:2%3c266:AID-JBM14%3e3.0.CO;2-B

    Article  CAS  PubMed  Google Scholar 

  58. Utech S, Prodanovic R, Mao AS, Ostafe R, Mooney DJ, Weitz DA (2015) Microfluidic generation of monodisperse, structurally homogeneous alginate microgels for cell encapsulation and 3D cell culture. Adv Healthc Mater 4:1628–1633. https://doi.org/10.1002/adhm.201500021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Huebner A, Srisa-Art M, Holt D, Abell C, Hollfelder F, Edel J (2007) Quantitative detection of protein expression in single cells using droplet microfluidics. Chem Commun 1218–1220. https://doi.org/10.1039/b618570c

  60. Martin K, Henkel T, Baier V, Grodrian A, Schön T, Roth M et al (2003) Generation of larger numbers of separated microbial populations by cultivation in segmented-flow microdevices. Lab Chip 3:202–207. https://doi.org/10.1039/B301258C

    Article  CAS  PubMed  Google Scholar 

  61. Brouzes E, Medkova M, Savenelli N, Marran D, Twardowski M, Hutchison JB et al (2009) Droplet microfluidic technology for single-cell high-throughput screening. Proc Natl Acad Sci USA 106:14195–14200. https://doi.org/10.1073/pnas.0903542106

    Article  PubMed  Google Scholar 

  62. Holtze C, Rowat A, Agresti J, Hutchison J, Angile F, Schmitz C et al (2008) Biocompatible surfactants for water-in-fluorocarbon emulsions. Lab Chip 8:1632–1639. https://doi.org/10.1039/B806706F

    Article  CAS  PubMed  Google Scholar 

  63. Li H-F, Pang Y-F, Liu J-J, Lin J-M (2011) Suspending nanoliter droplet arrays for cell capture and copper ion stimulation. Sens Actuators B Chem 155:415–421. https://doi.org/10.1016/j.snb.2010.12.023

    Article  CAS  Google Scholar 

  64. Song H, Bringer MR, Tice JD, Gerdts CJ, Ismagilov RF (2003) Experimental test of scaling of mixing by chaotic advection in droplets moving through microfluidic channels. Appl Phys Lett 83:4664–4666. https://doi.org/10.1063/1.1630378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Link D, Anna SL, Weitz D, Stone H (2004) Geometrically mediated breakup of drops in microfluidic devices. Phys Rev Lett 92:054503. https://doi.org/10.1103/physrevlett.92.054503

  66. Mazutis L, Gilbert J, Ung WL, Weitz DA, Griffiths AD, Heyman JA (2013) Single-cell analysis and sorting using droplet-based microfluidics. Nat Protoc 8:870–891. https://doi.org/10.1038/nprot.2013.046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Liu W, Chen Q, Lin X, Lin J-M (2015) Online multi-channel microfluidic chip-mass spectrometry and its application for quantifying noncovalent protein–protein interactions. Analyst 140:1551–1554. https://doi.org/10.1039/C4AN02370F

    Article  CAS  PubMed  Google Scholar 

  68. Rackus DG, Shamsi MH, Wheeler AR (2015) Electrochemistry, biosensors and microfluidics: a convergence of fields. Chem Soc Rev 44:5320–5340. https://doi.org/10.1039/C4CS00369A

    Article  CAS  PubMed  Google Scholar 

  69. Han Z, Li W, Huang Y, Zheng B (2009) Measuring rapid enzymatic kinetics by electrochemical method in droplet-based microfluidic devices with pneumatic valves. Anal Chem 81:5840–5845. https://doi.org/10.1021/ac900811y

    Article  CAS  PubMed  Google Scholar 

  70. Cecchini MP, Hong J, Lim C, Choo J, Albrecht T, deMello AJ et al (2011) Ultrafast surface enhanced resonance Raman scattering detection in droplet-based microfluidic systems. Anal Chem 83:3076–30781. https://doi.org/10.1021/ac103329b

    Article  CAS  PubMed  Google Scholar 

  71. Kang D-K, Ali MM, Zhang K, Pone EJ, Zhao W (2014) Droplet microfluidics for single-molecule and single-cell analysis in cancer research, diagnosis and therapy. Trends Anal Chem 58:145–153. https://doi.org/10.1016/j.trac.2014.03.006

    Article  CAS  Google Scholar 

  72. Kiss MM, Ortoleva-Donnelly L, Beer NR, Warner J, Bailey CG, Colston BW et al (2008) High-throughput quantitative polymerase chain reaction in picoliter droplets. Anal Chem 80:8975–8981. https://doi.org/10.1021/ac801276c

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Schaerli Y, Wootton RC, Robinson T, Stein V, Dunsby C, Neil MA et al (2008) Continuous-flow polymerase chain reaction of single-copy DNA in microfluidic microdroplets. Anal Chem 81:302–306. https://doi.org/10.1021/ac802038c

    Article  CAS  Google Scholar 

  74. 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 80:3522–3529. https://doi.org/10.1021/ac800327d

    Article  CAS  PubMed  Google Scholar 

  75. Han HS, Cantalupo PG, Rotem A, Cockrell SK, Carbonnaux M, Pipas JM et al (2015) Whole-genome sequencing of a single viral species from a highly heterogeneous sample. Angew Chem Int Ed 54:13985–13988. https://doi.org/10.1002/anie.201507047

    Article  CAS  Google Scholar 

  76. Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V et al (2015) Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:1187–1201. https://doi.org/10.1016/j.cell.2015.04.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pekin D, Skhiri Y, Baret J-C, Le Corre D, Mazutis L, Salem CB et al (2011) Quantitative and sensitive detection of rare mutations using droplet-based microfluidics. Lab Chip 11:2156–2166. https://doi.org/10.1039/C1LC20128J

    Article  CAS  PubMed  Google Scholar 

  78. Chao T-C, Ros A (2008) Microfluidic single-cell analysis of intracellular compounds. J R Soc Interface 5:139–150. https://doi.org/10.1098/rsif.2008.0233.focus

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  80. Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E et al (1998) Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 95:1735–1740. https://doi.org/10.1073/pnas.95.4.1735

    Article  CAS  PubMed  Google Scholar 

  81. Shahi P, Kim SC, Haliburton JR, Gartner ZJ, Abate AR (2017) Abseq: ultrahigh-throughput single cell protein profiling with droplet microfluidic barcoding. Sci Rep 7:44447. https://doi.org/10.1038/srep44447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Fallah-Araghi A, Baret J-C, Ryckelynck M, Griffiths AD (2012) A completely in vitro ultrahigh-throughput droplet-based microfluidic screening system for protein engineering and directed evolution. Lab Chip 12:882–891. https://doi.org/10.1039/C2LC21035E

    Article  CAS  PubMed  Google Scholar 

  83. Joensson HN, Samuels ML, Brouzes ER, Medkova M, Uhlén M, Link DR et al (2009) Detection and analysis of low-abundance cell-surface biomarkers using enzymatic amplification in microfluidic droplets. Angew Chem 121:2556–2559. https://doi.org/10.1002/anie.200804326

    Article  CAS  Google Scholar 

  84. Konry T, Smolina I, Yarmush JM, Irimia D, Yarmush ML (2011) Ultrasensitive detection of low-abundance surface-marker protein using isothermal rolling circle amplification in a microfluidic nanoliter platform. Small 7:395–400. https://doi.org/10.1002/smll.201001620

    Article  CAS  PubMed  Google Scholar 

  85. Giljohann DA, Mirkin CA (2009) Drivers of biodiagnostic development. Nature 462:461–464. https://doi.org/10.1038/nature08605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Del Ben F, Turetta M, Celetti G, Piruska A, Bulfoni M, Cesselli D et al (2016) A Method for detecting circulating tumor cells based on the measurement of single-cell metabolism in droplet-based microfluidics. Angew Chem 128:8723–8726. https://doi.org/10.1002/anie.201602328

    Article  CAS  Google Scholar 

  87. Chokkalingam V, Tel J, Wimmers F, Liu X, Semenov S, Thiele J et al (2013) Probing cellular heterogeneity in cytokine-secreting immune cells using droplet-based microfluidics. Lab Chip 13:4740–4744. https://doi.org/10.1039/C3LC50945A

    Article  CAS  PubMed  Google Scholar 

  88. Shim J-u, Ranasinghe RT, Smith CA, Ibrahim SM, Hollfelder F, Huck WT et al (2013) Ultrarapid generation of femtoliter microfluidic droplets for single-molecule-counting immunoassays. ACS Nano 7:5955–5964. https://doi.org/10.1021/nn401661d

    Article  CAS  PubMed  Google Scholar 

  89. Luo C, Ma Y, Li H, Chen F, Uchiyama K, Lin JM (2013) Generation of picoliter droplets of liquid for electrospray ionization with piezoelectric inkjet. J Mass Spectrom 48:321–328. https://doi.org/10.1002/jms.3159

    Article  CAS  PubMed  Google Scholar 

  90. Liu W, Wang N, Lin X, Ma Y, Lin JM (2014) Interfacing microsampling droplets and mass spectrometry by paper spray ionization for online chemical monitoring of cell culture. Anal Chem 86:7128–7134. https://doi.org/10.1021/ac501678q

    Article  CAS  PubMed  Google Scholar 

  91. Zhang W, Li N, Koga D, Zhang Y, Zeng H, Nakajima H et al (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 

  92. 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 Commun 54:2595–2598. https://doi.org/10.1039/C7CC09608A

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jin-Ming Lin .

Editor information

Editors and Affiliations

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

Chen, Q., Lin, JM. (2019). Droplet-Based Microfluidics for Single-Cell Encapsulation and Analysis. In: Lin, JM. (eds) Microfluidics for Single-Cell Analysis. Integrated Analytical Systems. Springer, Singapore. https://doi.org/10.1007/978-981-32-9729-6_5

Download citation

Publish with us

Policies and ethics