Skip to main content
SpringerLink
Log in

The good, the bad, and the tiny: a review of microflow cytometry

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Recent developments in microflow cytometry have concentrated on advancing technology in four main areas: (1) focusing the particles to be analyzed in the microfluidic channel, (2) miniaturization of the fluid-handling components, (3) miniaturization of the optics, and (4) integration and applications development. Strategies for focusing particles in a narrow path as they pass through the detection region include the use of focusing fluids, nozzles, and dielectrophoresis. Strategies for optics range from the use of microscope objectives to polymer waveguides or optical fibers embedded on-chip. While most investigators use off-chip fluidic control, there are a few examples of integrated valves and pumps. To date, demonstrations of applications are primarily used to establish that the microflow systems provide data of the same quality as laboratory systems, but new capabilities—such as automated sample staining—are beginning to emerge. Each of these four areas is discussed in detail in terms of the progress of development, the continuing limitations, and potential future directions for microflow cytometers.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Crosland-Taylor PJ (1953) Nature 171:37–38

    Article  CAS  Google Scholar 

  2. Steinkam J, Fulwyler MJ, Coulter JR, Hiebert RD, Horney JL, Mullaney PF (1973) Rev Sci Instrum 44:1301–1310

    Article  Google Scholar 

  3. Blankenstein G, Larsen UD (1998) Biosens Bioelectron 13:427–438

    Article  CAS  Google Scholar 

  4. Dubelaar GBJ, Geerders PJF, Jonker RR (2004) J Environ Monit 6:946–952

    Article  CAS  Google Scholar 

  5. Oh KW, Ahn CH (2006) J Micromechanics Microengineering 16:R13–R39

    Article  Google Scholar 

  6. Atencia J, Beebe DJ (2006) Lab Chip 6:567–574

    Article  CAS  Google Scholar 

  7. McClain MA, Culbertson CT, Jacobson SC, Allbritton NL, Sims CE, Ramsey JM (2003) Anal Chem 75:5646–5655

    Article  CAS  Google Scholar 

  8. Wang Z, El-Ali J, Engelund M, Gotsaed T, Perch-Nielsen IR, Mogensen KB, Snakenborg D, Kutter JP, Wolff A (2004) Lab Chip 4:372–377

    Article  CAS  Google Scholar 

  9. Wolff A, Perch-Nielsen IR, Larsen UD, Friis P, Goranovic G, Poulsen CR, Kutter JP, Telleman P (2003) Lab Chip 3:22–27

    Article  CAS  Google Scholar 

  10. Inatomi KI, Izuo SI, Lee SS (2006) Lett Appl Microbiol 43:296–300

    Article  Google Scholar 

  11. Kruger J, Singh K, O’Neill A, Jackson C, Morrison A, O’Brien P (2002) J Micromechanics Microengineering 12:486–494

    Article  Google Scholar 

  12. Lancaster C, Kokoris A, Nabavi M, Clemmens J, Maloney P, Capadanno J, Gerdes J, Battrell CF (2005) Methods 37:120–127

    Article  CAS  Google Scholar 

  13. Bernini R, De Nuccio E, Brescia F, Minardo A, Zeni L, Sarro PM, Palumbo R, Scarfi MR (2006) Anal Bioanal Chem 386:1267–1272

    Article  CAS  Google Scholar 

  14. Stiles T, Fallon R, Vestad T, Oakey J, Marr DWM, Squier J, Jimenez R (2005) Microfluidics and Nanofluidics 1:280–283

    Article  CAS  Google Scholar 

  15. Sun Y, Yin XF (2006) J Chromatogr A 1117:228–233

    Article  CAS  Google Scholar 

  16. Yao B, Luo GA, Feng X, Wang W, Chen LX, Wang YM (2004) Lab Chip 4:603–607

    Article  CAS  Google Scholar 

  17. Simonnet C, Groisman A (2006) Anal Chem 78:5653–5663

    Article  CAS  Google Scholar 

  18. Fu AY, Chou HP, Spence C, Arnold FH, Quake SR (2002) Anal Chem 74:2451–2457

    Article  CAS  Google Scholar 

  19. Yang SY, Hsiung SK, Hung YC, Chang CM, Liao TL, Lee GB (2006) Meas Sci Technol 17:2001–2009

    Article  CAS  Google Scholar 

  20. Wang C-H, Lee G-B (2006) J Micromechanics Microengineering 16:341–348.

    Article  CAS  Google Scholar 

  21. Xuan XC, Li DQ (2005) Electrophor 26:3552–3560

    Article  CAS  Google Scholar 

  22. Yang RJ, Chang CC, Huang SB, Lee GB (2005) J Micromechanics and Microengineering 15:2141–2148

    Article  CAS  Google Scholar 

  23. Jacobson SC, Ramsey JM (1997) Anal Chem 69:3212–3217

    Article  CAS  Google Scholar 

  24. Lee GB, Chang CC, Huang SB, Yang RJ (2006) J Micromechanics and Microengineering 16:1024–1032

    Article  Google Scholar 

  25. McClain MA, Culbertson CT, Jacobson SC, Ramsey JM (2001) Anal Chem 73:5334–5338

    Article  CAS  Google Scholar 

  26. Krishnamoorthy S, Feng J, Henry AC, Locascio LE, Hickman JJ, Sundaram S (2006) Microfluidics and Nanofluidics 2:345–355

    Article  CAS  Google Scholar 

  27. Eyal S, Quake SR (2002) Electrophor 23:2653–2657

    Article  CAS  Google Scholar 

  28. Munyan JW, Fuentes HV, Draper M, Kelly RT, Woolley AT (2003) Lab Chip 3:217–220

    Article  CAS  Google Scholar 

  29. Singh K, Su XT, Liu CG, Capjack C, Rozmus W, Backhouse CJ (2006) Cytometry Part A 69A:307–315

    Article  Google Scholar 

  30. Gawad S, Schild L, Renaud P (2001) Lab Chip 1:76–82

    Article  CAS  Google Scholar 

  31. Fu AY, Spence C, Scherer A, Arnold FH, Quake SR (1999) Nature Biotechnol 17:1109–1111

    Article  CAS  Google Scholar 

  32. Lien V, Zhao K, Berdichevsky Y, Lo YH (2005) IEEE J Sel Top Quantum Electron 11:827–834

    Article  CAS  Google Scholar 

  33. Stavis SM, Edel JB, Samiee KT, Craighead HG (2005) Lab Chip 5:337–343

    Article  CAS  Google Scholar 

  34. Xiang Q, Xuan XC, Xu B, Li, DQ (2005) Instrum Sci Technol 33:597–607

    Article  CAS  Google Scholar 

  35. Godin J, Lien V, Lo YH (2006) Appl Phys Lett 89

  36. Perry H, Greiner C, Georgakoudi I, Cronin-Golomb M, Omenetto FG (2007) Rev Sci Instrum 78

  37. Wood DK, Braun GB, Fraikin JL, Swenson LJ, Reich NO, Cleland AN (2007) Lab Chip 7:469–474

    Article  CAS  Google Scholar 

  38. Tung YC, Zhang M, Lin CT, Kurabayashi K, Skerlos SJ (2004) Sens Actuators, B, Chem 98:356–367

    Article  Google Scholar 

  39. Dittrich PS, Schwille P (2003) Anal Chem 75:5767–5774

    Article  CAS  Google Scholar 

  40. Li PCH, Harrison DJ (1997) Anal Chem 69:1564–1568

    Article  CAS  Google Scholar 

  41. Schrum DP, Culbertson CT, Jacobson SC, Ramsey JM (1999) Anal Chem 71:4173–4177

    Article  CAS  Google Scholar 

  42. Sundararajan N, Pio MS, Lee LP, Berlin AA (2004) J Microelectromechanical Syst 13:559–567

    Article  Google Scholar 

  43. Blankenstein G, Scampavia LD, Ruzicka J, Christian GD (1996) Cytometry 25:200–204

    Article  CAS  Google Scholar 

  44. Lee GB, Lin CH, Chang GL (2003) Sens Actuators A, Phys 103:165–170

    Article  Google Scholar 

  45. Pamme N, Koyama R, Manz A (2003) Lab Chip 3:187–192

    Article  CAS  Google Scholar 

  46. Chung S, Park SJ, Kim JK, Chung C, Han DC, Chang JK (2003) Microsystem Technologies-Micro-and Nanosystems-Information Storage and Processing Systems 9:525–533

    Google Scholar 

  47. Fu LM, Yang RJ, Lin CH, Pan YJ, Lee GB (2004) Anal Chim Acta 507:163–169

    Article  CAS  Google Scholar 

  48. Huh D, Gu W, Kamotani Y, Grotberg JB, Takayama S (2005) Physiol Meas 26:R73–R98

    Article  Google Scholar 

  49. Simonnet C, Groisman A (2005) Appl Phys Lett 87

  50. Chang CC, Huang ZX, Yang RJ (2007) J Micromechanics and Microengineering 17:1479–1486

    Article  CAS  Google Scholar 

  51. Klank H, Goranovic G, Kutter JP, Gjelstrup H, Michelsen J, Westergaard CH (2002) J Micromechanics and Microengineering 12:862–869

    Article  Google Scholar 

  52. Yang R, Feeback DL, Wang WJ (2005) Sens Actuators A, Phys 118:259–267

    Article  Google Scholar 

  53. Goranovic G, Perch-Nielson IR, Larsen UD, Wolff A, Kutter JP, Telleman P (2001) In Modeling and Simulation of Microsystems

  54. Bang HW, Yun HY, Lee WG, Park J, Lee J, Chung S, Cho K, Chung C, Han DC, Chang JK (2006) Lab Chip 6:1381–1383

    Article  CAS  Google Scholar 

  55. Lin CH, Lee GB, Fu LM, Hwey BH (2004) J Microelectromechanical Systems 13:923–932

    Article  Google Scholar 

  56. Holmes D, Morgan H, Green NG (2006) Biosensors Bioelectronics 21:1621–1630

    Article  CAS  Google Scholar 

  57. Mogensen KB, Petersen NJ, Hubner J, Kutter JR (2001) Electrophor 22:3930–3938

    Article  CAS  Google Scholar 

  58. Verpoorte E (2003) Lab Chip 3:42N–52N

    Article  CAS  Google Scholar 

  59. Wu MH, Wang JB, Taha T, Cui ZF, Urban JPG, Cui Z (2007) Biomedical Microdevices 9:167–174

    Article  CAS  Google Scholar 

  60. Lien V (2006) IEEE Photonics Technol Lett 16:1525–1527

    Article  Google Scholar 

  61. Chang-Yen DA, Eich RK, Gale BK (2005) J Lightwave Technol 23:2088

    Article  CAS  Google Scholar 

  62. Friis P, Hoppe K, Leistiko O, Mogensen KB, Hübner J, Kutter JP (2001) Appl Opt 40:6246–6251

    Article  CAS  Google Scholar 

  63. Ruano JM, Benoit V, Aitchison JS, Cooper JM (2000) Anal Chem 72:1093–1097

    Article  CAS  Google Scholar 

  64. Ladouceur F (1997) J Lightwave Technol 15:1020–1025

    Article  CAS  Google Scholar 

  65. Grewe M, Grosse A, Fouckhardt H (2000) Appl Phys B-Lasers and Optics 70:839–847

    CAS  Google Scholar 

  66. Said AA, Dugan M, Bado P, Bellouard Y, Scott A, Mabesa JJR (2004) in Photon Processing in Microelectronics and Photonics III 5339:194–204, SPIE, San Jose, Ca, USA

    Google Scholar 

  67. Kamei T, Paegel BM, Scherer JR, Skelley AM, Street RA, Mathies RA (2003) Anal Chem 75:5300–5305

    Article  CAS  Google Scholar 

  68. Chen CH, Tsai F, Lien V, Justis N, Lo YH (2007) IEEE Photonics Technol Lett 19:441–443

    Article  Google Scholar 

  69. Nieuwenhuis JH, Bastemeijer J, Bossche A, Vellekoop MJ (2003) IEEE Sens J 3:646–651

    Article  CAS  Google Scholar 

  70. Hartley L, Kaler K, Yadid-Pecht O (2007) IEEE Trans Circuits Syst I-Regular Papers 54:99–110

    Article  Google Scholar 

  71. Camou S, Fujita H, Fujii T (2003) Lab Chip 3:40–45

    Article  CAS  Google Scholar 

  72. Kuo JN, Hsieh CC, Yang SY, Lee GB (2007) J Micromechanics and Microengineering 17:693–699

    Article  Google Scholar 

  73. Traut S, Rossi M, Herzig HP (2000) J Mod Opt 47:2391–2397

    CAS  Google Scholar 

  74. Nussbaum P, Philipoussis I, Husser A, Herzig HP (1998) Opt Eng 37:1804–1808

    Article  Google Scholar 

  75. Novak L, Neuzil P, Pipper J, Zhang Y, Lee S (2007) Lab Chip 7:27–29

    Article  CAS  Google Scholar 

  76. Balslev S, Jorgensen AM, Bilenberg B, Mogensen KB, Snakenborg D, Geschke O, Kutter JP, Kristensen A (2006) Lab Chip 6:213–217

    Article  CAS  Google Scholar 

  77. Hofmann O, Wang X, Cornwell A, Beecher S, Raja A, Bradley DD, Demello AJ, Demello JC (2006) Lab Chip 6:981–987

    Article  CAS  Google Scholar 

  78. Burns MA, Johnson BN, Brahmasandra SN, Handique K, Webster JR, Krishnan M, Sammarco TS, Man PM, Jones D, Heldsinger D, Mastrangelo CH, Burke DT (1998) Science 282:484–487

    Article  CAS  Google Scholar 

  79. Adams ML, Enzelberger M, Quake S, Scherer A (2003) Sens Actuators A-Phys 104:25–31

    Article  Google Scholar 

  80. Chediak JA, Luo ZS, Seo JG, Cheung N, Lee LP, Sands TD (2004) Sens Actuators A-Phys 111:1–7

    Article  Google Scholar 

  81. Snow C (2004) Cytom Part A 57A:63–69

    Article  Google Scholar 

  82. Cheung K, Gawad S, Renaud P (2005) Cytom Part A 65A:124–132

    Article  CAS  Google Scholar 

  83. Chun HG, Chung TD, Kim HC (2005) Anal Chem 77:2490–2495

    Article  CAS  Google Scholar 

  84. Sims CE, Allbritton NL (2007) Lab Chip 7:423–440

    Article  CAS  Google Scholar 

  85. Chen X, Cui DF, Liu CC, Li H, Chen J (2007) Anal Chim Acta 584:237–243

    Article  CAS  Google Scholar 

  86. Thorslund S, Klett O, Nikolajeff F, Markides K, Bergquist J (2006) Biomedical Microdevices 8:73–79

    Article  CAS  Google Scholar 

  87. Chang CM, Hsiung SK, Lee GB (2007) Jpn J Appl Phys 46:3126–3134

    Google Scholar 

  88. Preckel T, Luedke G, Chan SDH, Wang BN, Dubrow R, Buhlmann C (2002) J Assoc Lab Autom 7:85–89

    Article  CAS  Google Scholar 

  89. Chan SDH, Luedke G, Valer M, Buhlmann C, Preckel T (2003) Cytom Part A 55A:119–125

    Article  CAS  Google Scholar 

  90. Yamaguchi N, Ohba H, Nasu M (2006) Lett Appl Microbiol 43:631–636

    Article  CAS  Google Scholar 

  91. Gerdts G, Luedke G (2006) J Microbiological Methods 64:232–240

    Article  CAS  Google Scholar 

  92. Wang MM, Tu E, Raymond DE, Yang JM, Zhang HC, Hagen N, Dees B, Mercer EM, Forster AH, Kariv I, Marchand PJ, Butler WF (2005) Nature Biotechnol 23:83–87

    Article  CAS  Google Scholar 

  93. Sakamoto C, Yamaguchi N, Yamada M, Nagase H, Seki M, Nasu M (2007) J Microbiological Methods 68:643–647

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The preparation of this manuscript was supported by NRL/ONR 6.2 Work Unit 6006. DAA and LRH are National Research Council Postdoctoral Fellows. The views are those of the authors and do not reflect policy or opinion of the US Navy or Department of Defense.

Author information

Authors and Affiliations

  1. Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, DC, 20375, USA

    Daniel A. Ateya, Jeffrey S. Erickson, Peter B. Howell Jr, Lisa R. Hilliard, Joel P. Golden & Frances S. Ligler

Authors
  1. Daniel A. Ateya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeffrey S. Erickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter B. Howell Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lisa R. Hilliard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joel P. Golden
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Frances S. Ligler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frances S. Ligler.

Additional information

Jeffrey S. Erickson, Peter B. Howell Jr and Daniel A. Ateya, provided equivalent contributions to this review.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ateya, D.A., Erickson, J.S., Howell, P.B. et al. The good, the bad, and the tiny: a review of microflow cytometry. Anal Bioanal Chem 391, 1485–1498 (2008). https://doi.org/10.1007/s00216-007-1827-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-007-1827-5

Keywords

Search

Navigation