Skip to main content

Advertisement

SpringerLink
Log in

High-throughput, multiparameter analysis of single cells

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

Abstract

Heterogeneity of cell populations in various biological systems has been widely recognized, and the highly heterogeneous nature of cancer cells has been emerging with clinical relevance. Single-cell analysis using a combination of high-throughput and multiparameter approaches is capable of reflecting cell-to-cell variability, and at the same time of unraveling the complexity and interdependence of cellular processes in the individual cells of a heterogeneous population. In this review, analytical methods and microfluidic tools commonly used for high-throughput, multiparameter single-cell analysis of DNA, RNA, and proteins are discussed. Applications and limitations of currently available technologies for cancer research and diagnostics are reviewed in the light of the ultimate goal to establish clinically applicable assays.

ᅟ

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

Similar content being viewed by others

References

  1. Kalisky T, Quake SR (2011) Nat Methods 8:311–314

    CAS  Google Scholar 

  2. Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Science 297:1183–1186

    CAS  Google Scholar 

  3. Huang S (2009) Development 136:3853–3862

    CAS  Google Scholar 

  4. Muzzey D, van Oudenaarden A (2009) Annu Rev Cell Dev Biol 25:301–327

    CAS  Google Scholar 

  5. Oates AC, Gorfinkiel N, González-Gaitán M, Heisenberg CP (2009) Nat Rev Genet 10:517–530

    CAS  Google Scholar 

  6. El Debs B, Utharala R, Balyasnikova IV, Griffiths AD, Merten CA (2012) Proc Natl Acad Sci U S A 109:11570–11575

    Google Scholar 

  7. Kida A, Iijima M, Niimi T, Maturana AD, Yoshimoto N, Kuroda S (2013) Anal Chem 85:1753–1759

    CAS  Google Scholar 

  8. Kromenaker SJ, Srienc F (1994) Biotechnol Prog 10:299–307

    CAS  Google Scholar 

  9. Musat N, Halm H, Winterholler B, Hoppe P, Peduzzi S, Hillion F, Horreard F, Amann R, Jørgensen BB, Kuypers MMM (2008) Proc Natl Acad Sci U S A 105:17861–17866

    CAS  Google Scholar 

  10. Zong C, Lu S, Chapman AR, Xie XS (2012) Science 338:1622–1626

    CAS  Google Scholar 

  11. Pester M, Brambilla E, Alazard D, Rattei T, Weinmaier T, Han J, Lucas S, Lapidus A, Cheng JF, Goodwin L, Pitluck S, Peters L, Ovchinnikova G, Teshima H, Detter JC, Han CS, Tapia R, Land ML, Hauser L, Kyrpides NC, Ivanova NN, Pagani I, Huntmann M, Wei CL, Davenport KW, Daligault H, Chain PSG, Chen A, Mavromatis K, Markowitz V, Szeto E, Mikhailova N, Pati A, Wagner M, Woyke T, Ollivier B, Klenk HP, Spring S, Loy A (2012) J Bacteriol 194:6300–6301

    CAS  Google Scholar 

  12. Spits C, Le Caignec C, De Rycke M, Van Haute L, Van Steirteghem A, Liebaers I, Sermon K (2006) Nat Protoc 1:1965–1970

    CAS  Google Scholar 

  13. Ozsolak F (2012) Expert Opin Drug Discov 7:231–243

    CAS  Google Scholar 

  14. Wang J, Fan HC, Behr B, Quake SR (2012) Cell 150:402–412

    CAS  Google Scholar 

  15. Fan HC, Wang J, Potanina A, Quake SR (2011) Nat Biotechnol 29:51–57

    CAS  Google Scholar 

  16. Swerdlow H, Wu SL, Harke H, Dovichi NJ (1990) J Chromatogr 516:61–67

    CAS  Google Scholar 

  17. Liu L, Li Y, Li S, Hu N, He Y, Pong R, Lin D, Lu L, Law M (2012) J Biomed Biotechnol 2012:251364

    Google Scholar 

  18. Shendure J, Ji H (2008) Nat Biotechnol 26:1135–1145

    CAS  Google Scholar 

  19. Rothberg JM, Leamon JH (2008) Nat Biotechnol 26:1117–1124

    CAS  Google Scholar 

  20. Wang D, Bodovitz S (2010) Trends Biotechnol 28:281–290

    CAS  Google Scholar 

  21. Schadt EE, Turner S, Kasarskis A (2010) Hum Mol Genet 19:R227–R240

    CAS  Google Scholar 

  22. Lipson D, Raz T, Kieu A, Jones DR, Giladi E, Thayer E, Thompson JF, Letovsky S, Milos P, Causey M (2009) Nat Biotechnol 27:652–658

    CAS  Google Scholar 

  23. Thompson JF, Steinmann KE (2010) Curr Protoc Mol Biol Chapt 7:Unit7.10

    Google Scholar 

  24. Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, Peluso P, Rank D, Baybayan P, Bettman B, Bibillo A, Bjornson K, Chaudhuri B, Christians F, Cicero R, Clark S, Dalal R, Dewinter A, Dixon J, Foquet M, Gaertner A, Hardenbol P, Heiner C, Hester K, Holden D, Kearns G, Kong X, Kuse R, Lacroix Y, Lin S, Lundquist P, Ma C, Marks P, Maxham M, Murphy D, Park I, Pham T, Phillips M, Roy J, Sebra R, Shen G, Sorenson J, Tomaney A, Travers K, Trulson M, Vieceli J, Wegener J, Wu D, Yang A, Zaccarin D, Zhao P, Zhong F, Korlach J, Turner S (2009) Science 323:133–138

    CAS  Google Scholar 

  25. Lewis T (2012) Genome on a Stick. BioTechniques News

  26. Hayden EC (2012) Nanopore genome sequencer makes its debut. Nature News doi:10.1038/nature.2012.10051

  27. Mamanova L, Coffey AJ, Scott CE, Kozarewa I, Turner EH, Kumar A, Howard E, Shendure J, Turner DJ (2010) Nat Methods 7:111–118

    CAS  Google Scholar 

  28. Mertes F, Elsharawy A, Sauer S, van Helvoort JMLM, van der Zaag PJ, Franke A, Nilsson M, Lehrach H, Brookes AJ (2011) Brief Funct Genomics 10:374–386

    CAS  Google Scholar 

  29. Cummings N, King R, Rickers A, Kaspi A, Lunke S, Haviv I, Jowett JBM (2010) BMC Genomics 11:641

    Google Scholar 

  30. Coissac E (2012) Methods Mol Biol 888:13–31

    Google Scholar 

  31. Islam S, Kjällquist U, Moliner A, Zajac P, Fan JB, Lönnerberg P, Linnarsson S (2011) Genome Res 21:1160–1167

    CAS  Google Scholar 

  32. Hebenstreit D (2012) Biology 1:658–667

    CAS  Google Scholar 

  33. Tang F, Lao K, Surani MA (2011) Nat Methods 8:S6–S11

    CAS  Google Scholar 

  34. Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O, Wendler N, Passlick B, Huber RM, Schlimok G, Baeuerle PA, Riethmüller G (2002) Nat Biotechnol 20:387–392

    CAS  Google Scholar 

  35. Sul JY, Wen K, Wu C, Zeng F, Jochems J, Lee MT, Kim TK, Peritz T, Buckley P, Cappelleri DJ, Maronski M, Kim M, Kumar V, Meaney D, Kim J, Eberwine J (2009) Proc Natl Acad Sci U S A 106:7624–7629

    CAS  Google Scholar 

  36. Kurimoto K, Yabuta Y, Ohinata Y, Ono Y, Uno KD, Yamada RG, Ueda HR, Saitou M (2006) Nucleic Acids Res 34:e42

    Google Scholar 

  37. Wagner GP, Kin K, Lynch VJ (2012) Theory Biosci 131:281–285

    CAS  Google Scholar 

  38. Hashimshony T, Wagner F, Sher N, Yanai I (2012) Cell Rep 2:666–673

    CAS  Google Scholar 

  39. Smith AM, Heisler LE, St Onge RP, Farias-Hesson E, Wallace IM, Bodeau J, Harris AN, Perry KM, Giaever G, Pourmand N, Nislow C (2010) Nucleic Acids Res 38:e142

    Google Scholar 

  40. Shiroguchi K, Jia TZ, Sims PA, Xie XS (2012) Proc Natl Acad Sci U S A 109:1347–1352

    CAS  Google Scholar 

  41. Taniguchi K, Kajiyama T, Kambara H (2009) Nat Methods 6:503–506

    CAS  Google Scholar 

  42. Faragó N, Kocsis GK, Lovas S, Molnár G, Boldog E, Rózsa M, Szemenyei V, Vámos E, Nagy LI, Tamás G, Puskás LG (2013) Biotechniques 54:327–336

    Google Scholar 

  43. Warren L, Bryder D, Weissman IL, Quake SR (2006) Proc Natl Acad Sci U S A 103:17807–17812

    CAS  Google Scholar 

  44. Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S (2006) PLoS Biol 4:e309

    Google Scholar 

  45. Fu GK, Hu J, Wang PH, Fodor SPA (2011) Proc Natl Acad Sci U S A 108:9026–9031

    CAS  Google Scholar 

  46. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, Dunaway DL, Fell HP, Ferree S, George RD, Grogan T, James JJ, Maysuria M, Mitton JD, Oliveri P, Osborn JL, Peng T, Ratcliffe AL, Webster PJ, Davidson EH, Hood L (2008) Nat Biotechnol 26:317–325

    CAS  Google Scholar 

  47. Wu M, Singh AK (2012) Curr Opin Biotechnol 23:83–88

    CAS  Google Scholar 

  48. Cooper G, Hausman R (2007) The cell, 4th edn. ASM, Washington, DC

    Google Scholar 

  49. Rauch P, Angela Z, Nico D, Christoph S, Sperling D (2005) Laborwelt 4:2–6

    Google Scholar 

  50. Kraemer S, Vaught JD, Bock C, Gold L, Katilius E, Keeney TR, Kim N, Saccomano NA, Wilcox SK, Zichi D, Sanders GM (2011) PLoS One 6:e26332

    CAS  Google Scholar 

  51. Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK (2012) Trends Immunol 33:323–332

    CAS  Google Scholar 

  52. De Rosa SC, Herzenberg LA, Herzenberg LA, Roederer M (2001) Nat Med 7:245–248

    Google Scholar 

  53. Perez OD, Nolan GP (2002) Nat Biotechnol 20:155–162

    CAS  Google Scholar 

  54. Perfetto SP, Chattopadhyay PK, Roederer M (2004) Nat Rev Immunol 4:648–655

    CAS  Google Scholar 

  55. Ornatsky O, Bandura D, Baranov V, Nitz M, Winnik MA, Tanner S (2010) J Immunol Methods 361:1–20

    CAS  Google Scholar 

  56. Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud y, Gjertsen BT, Nolan GP (2004) Cell 118:217–228

    CAS  Google Scholar 

  57. Krutzik PO, Nolan GP (2006) Nat Methods 3:361–368

    CAS  Google Scholar 

  58. Clutter MR, Heffner GC, Krutzik PO, Sachen KL, Nolan GP (2010) Cytometry A 77:1020–1031

    Google Scholar 

  59. Black CB, Duensing TD, Trinkle LS, Dunlay RT (2011) Assay Drug Dev Technol 9:13–20

    CAS  Google Scholar 

  60. Mao X, Nawaz AA, Lin SCS, Lapsley MI, Zhao Y, McCoy JP, El-Deiry WS, Huang TJ (2012) Biomicrofluidics 6:24113–241139

    Google Scholar 

  61. Cheung KC, Di Berardino M, Schade-Kampmann G, Hebeisen M, Pierzchalski A, Bocsi J, Mittag A, Tárnok A (2010) Cytometry A 77:648–666

    Google Scholar 

  62. Su X, Kirkwood SE, Gupta M, Marquez-Curtis L, Qiu Y, Janowska-Wieczorek A, Rozmus W, Tsui YY (2011) Opt Express 19:387–398

    CAS  Google Scholar 

  63. Srivastava N, Brennan JS, Renzi RF, Wu M, Branda SS, Singh AK, Herr AE (2009) Anal Chem 81:3261–3269

    CAS  Google Scholar 

  64. Song H, Wang Y, Rosano JM, Prabhakarpandian B, Garson C, Pant K, Lai E (2013) Lab Chip 13:2300–2310

    CAS  Google Scholar 

  65. Baret JC, Miller OJ, Taly V, Ryckelynck M, El-Harrak A, Frenz L, Rick C, Samuels ML, Hutchison JB, Agresti JJ, Link DR, Weitz DA, Griffiths AD (2009) Lab Chip 9:1850–1858

    CAS  Google Scholar 

  66. Mullard A (2011) Nat Rev Drug Discov 10:477–478

    CAS  Google Scholar 

  67. Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Anal Chem 81:6813–6822

    CAS  Google Scholar 

  68. Bendall SC, Nolan GP (2012) Nat Biotechnol 30:639–647

    CAS  Google Scholar 

  69. Bendall SC, Simonds EF, Qiu P, Amir ED, Krutzik PO, Finck R, Bruggner RV, Melamed R, Trejo A, Ornatsky OI, Balderas RS, Plevritis SK, Sachs K, Pe’er D, Tanner SD, Nolan GP (2011) Science 332:687–696

    CAS  Google Scholar 

  70. Basiji DA, Ortyn WE, Liang L, Venkatachalam V, Morrissey P (2007) Clin Lab Med 27:653–670, viii

    Google Scholar 

  71. Schroeder T (2011) Nat Methods 8:S30–S35

    CAS  Google Scholar 

  72. Pepperkok R, Ellenberg J (2006) Nat Rev Mol Cell Biol 7:690–696

    CAS  Google Scholar 

  73. Oheim M (2007) Br J Pharmacol 152:1–4

    CAS  Google Scholar 

  74. Harnett MM (2007) Nat Rev Immunol 7:897–904

    CAS  Google Scholar 

  75. Mavroudis D (2010) Ann Oncology 21:vii95–vii100

    Google Scholar 

  76. Goda K, Ayazi A, Gossett DR, Sadasivam J, Lonappan CK, Sollier E, Fard AM, Hur SC, Adam J, Murray C, Wang C, Brackbill N, Di Carlo D, Jalali B (2012) Proc Natl Acad Sci U S A 109:11630–11635

    CAS  Google Scholar 

  77. Lee P, Gaige T, Hung P (2011) Methods Cell Biol 102:77–103

    Google Scholar 

  78. Skafte-Pedersen P, Hemmingsen M, Sabourin D, Blaga FS, Bruus H, Dufva M (2012) Biomed Microdevices 14:385–399

    CAS  Google Scholar 

  79. Schubert W, Bonnekoh B, Pommer AJ, Philipsen L, Bckelmann R, Malykh Y, Gollnick H, Friedenberger M, Bode M, Dress AWM (2006) Nat Biotechnol 24:1270–1278

    CAS  Google Scholar 

  80. Han Q, Bradshaw EM, Nilsson B, Hafler DA, Love JC (2010) Lab Chip 10:1391–1400

    CAS  Google Scholar 

  81. Jones CN, Lee JY, Zhu J, Stybayeva G, Ramanculov E, Zern MA, Revzin A (2008) Anal Chem 80:6351–6357

    CAS  Google Scholar 

  82. Alix-Panabières C (2012) Recent Results Cancer Res 195:69–76

    Google Scholar 

  83. Ma C, Fan R, Ahmad H, Shi Q, Comin-Anduix B, Chodon T, Koya RC, Liu CC, Kwong GA, Radu CG, Ribas A, Heath JR (2011) Nat Med 17:738–743

    CAS  Google Scholar 

  84. Choi J, Love KR, Gong Y, Gierahn TM, Love JC (2011) Anal Chem 83:6890–6895

    CAS  Google Scholar 

  85. Huang B, Wu H, Bhaya D, Grossman A, Granier S, Kobilka BK, Zare RN (2007) Science 315:81–84

    CAS  Google Scholar 

  86. Salehi-Reyhani A, Kaplinsky J, Burgin E, Novakova M, Demello AJ, Templer RH, Parker P, Neil MAA, Ces O, French P, Willison KR, Klug D (2011) Lab Chip 11:1256–1261

    CAS  Google Scholar 

  87. Mellors JS, Jorabchi K, Smith LM, Ramsey JM (2010) Anal Chem 82:967–973

    CAS  Google Scholar 

  88. Urban PL, Jefimovs K, Amantonico A, Fagerer SR, Schmid T, Mädler S, Puigmarti-Luis J, Goedecke N, Zenobi R (2010) Lab Chip 10:3206–3209

    CAS  Google Scholar 

  89. Velve-Casquillas G, Le Berre M, Piel M, Tran PT (2010) Nano Today 5:28–47

    CAS  Google Scholar 

  90. Ren K, Zhou J, Wu H (2013) Acc Chem Res 46:2396–2406

    Google Scholar 

  91. Lenshof A, Laurell T (2010) Chem Soc Rev 39:1203–1217

    CAS  Google Scholar 

  92. Gossett DR, Weaver WM, Mach AJ, Hur SC, Tse HTK, Lee W, Amini H, Carlo DD (2010) Anal Bioanal Chem 397:3249–3267

    CAS  Google Scholar 

  93. Nilsson J, Evander M, Hammarström B, Laurell T (2009) Anal Chim Acta 649:141–157

    CAS  Google Scholar 

  94. Lindström S, Eriksson M, Vazin T, Sandberg J, Lundeberg J, Frisén J, Andersson-Svahn H (2009) PLoS One 4:e6997

    Google Scholar 

  95. Ashton RS, Peltier J, Fasano CA, O’Neill A, Leonard J, Temple S, Schaffer DV, Kane RS (2007) Stem Cells 25:2928–2935

    CAS  Google Scholar 

  96. Lindström S, Andersson-Svahn H (2011) Biochim Biophys Acta 1810:308–316

    Google Scholar 

  97. Rettig JR, Folch A (2005) Anal Chem 77:5628–5634

    CAS  Google Scholar 

  98. Yun KS, Lee D, Kim HS, Yoon E (2009) Sens Actuators B Chem 143:387–394

    Google Scholar 

  99. Jen CP, Hsiao JH, Maslov NA (2012) Sensors (Basel) 12:347–358

    CAS  Google Scholar 

  100. Eyer K, Kuhn P, Hanke C, Dittrich PS (2012) Lab Chip 12:765–772

    CAS  Google Scholar 

  101. Carlo DD, Lee LP (2006) Anal Chem 78:7918–7925

    Google Scholar 

  102. Chung J, Kim YJ, Yoon E (2011) Appl Phys Lett 98:123701

    Google Scholar 

  103. Zheng S, Lin H, Liu JQ, Balic M, Datar R, Cote RJ, Tai YC (2007) J Chromatogr A 1162:154–161

    CAS  Google Scholar 

  104. Karimi A, Yazdi S, Ardekani AM (2013) Biomicrofluidics 7:021501

    Google Scholar 

  105. Stott SL, Hsu CH, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK et al (2010) Proc Natl Acad Sci 107:18392–18397

    CAS  Google Scholar 

  106. Zhang H, Liu KK (2008) J R Soc Interface 5:671–690

    CAS  Google Scholar 

  107. Park H, Kim D, Yun KS (2010) Sens Actuators B Chem 150:167–173

    CAS  Google Scholar 

  108. Chuang CH, Huang YW, Wu YT (2012) Biomed Microdevices 14:271–278

    CAS  Google Scholar 

  109. Valley J, Ohta A, Hsu HY, Neale S, Jamshidi A, Wu M (2009) IEEE Trans Biomed Circuits Syst 3:424–431

    CAS  Google Scholar 

  110. Augustsson P, Magnusson C, Nordin M, Lilja H, Laurell T (2012) Anal Chem 84:7954–7962

    CAS  Google Scholar 

  111. Yang F, Yang X, Jiang H, Bulkhaults P, Wood P, Hrushesky W, Wang G (2010) Biomicrofluidics 4:013204

    Google Scholar 

  112. Thorsen T, Roberts RW, Arnold FH, Quake SR (2001) Phys Rev Lett 86:4163–4166

    CAS  Google Scholar 

  113. Anna SL, Bontoux N, Stone HA (2003) Appl Phys Lett 82:364

    CAS  Google Scholar 

  114. Ahn K, Kerbage C, Hunt TP, Westervelt RM, Link DR, Weitz DA (2006) Appl Phys Lett 88:024104

    Google Scholar 

  115. Abate AR, Hung T, Mary P, Agresti JJ, Weitz DA (2010) Proc Natl Acad Sci U S A 107:19163–19166

    CAS  Google Scholar 

  116. Ahn K, Agresti J, Chong H, Marquez M, Weitz DA (2006) Appl Phys Lett 88:264105

    Google Scholar 

  117. Song H, Bringer MR, Tice JD, Gerdts CJ, Ismagilov RF (2003) Appl Phys Lett 83:4664–4666

    CAS  Google Scholar 

  118. Tice JD, Song H, Lyon AD, Ismagilov RF (2003) Langmuir 19:9127–9133

    CAS  Google Scholar 

  119. Link DR, Anna SL, Weitz DA, Stone HA (2004) Phys Rev Lett 92:054503

    CAS  Google Scholar 

  120. Brouzes E, Medkova M, Savenelli N, Marran D, Twardowski M, Hutchison JB, Rothberg JM, Link DR, Perrimon N, Samuels ML (2009) Proc Natl Acad Sci U S A 106:14195–14200

    CAS  Google Scholar 

  121. Frenz L, Blank K, Brouzes E, Griffiths AD (2009) Lab Chip 9:1344

    CAS  Google Scholar 

  122. Holtze C, Rowat AC, Agresti JJ, Hutchison JB, Angilè FE, Schmitz CHJ, Köster S, Duan H, Humphry KJ, Scanga RA, Johnson JS, Pisignano D, Weitz DA (2008) Lab Chip 8:1632–1639

    CAS  Google Scholar 

  123. Schmitz CHJ, Rowat AC, Köster S, Weitz DA (2009) Lab Chip 9:44–49

    CAS  Google Scholar 

  124. Shim JU, Cristobal G, Link DR, Thorsen T, Jia Y, Piattelli K, Fraden S (2007) J Am Chem Soc 129:8825–8835

    CAS  Google Scholar 

  125. Shim J, Olguin LF, Whyte G, Scott D, Babtie A, Abell C, Huck WTS, Hollfelder F (2009) J Am Chem Soc 131:15251–15256

    CAS  Google Scholar 

  126. Link DR, Grasland-Mongrain E, Duri A, Sarrazin F, Cheng Z, Cristobal G, Marquez M, Weitz DA (2006) Angew Chem Int Ed 45:2556–2560

    Google Scholar 

  127. Baroud CN, Delville JP, Gallaire F, Wunenburger R (2007) Phys Rev E Stat Nonlin Soft Matter Phys 75:046302

    Google Scholar 

  128. Chabert M, Viovy JL (2008) Proc Natl Acad Sci U S A 105:3191–3196

    CAS  Google Scholar 

  129. Clausell-Tormos J, Lieber D, Baret JC, El-Harrak A, Miller OJ, Frenz L, Blouwolff J, Humphry KJ, Köster S, Duan H, Holtze C, Weitz DA, Griffiths AD, Merten CA (2008) Chem Biol 15:427–437

    CAS  Google Scholar 

  130. Chen Y, Wijaya Gani A, Tang SKY (2012) Lab Chip 12:5093–5103

    CAS  Google Scholar 

  131. Huebner A, Srisa-Art M, Holt D, Abell C, Hollfelder F, deMello AJ, Edel JB (2007) Chem Commun 1218–1220

  132. Lindström S, Andersson-Svahn H (2010) Lab Chip 10:3363–3372

    Google Scholar 

  133. Edd JF, Carlo DD, Humphry KJ, Köster S, Irimia D, Weitz DA, Toner M (2008) Lab Chip 8:1262–1264

    CAS  Google Scholar 

  134. Tawfik DS, Griffiths AD (1998) Nat Biotechnol 16:652–656

    CAS  Google Scholar 

  135. Kiss MM, Ortoleva-Donnelly L, Beer NR, Warner J, Bailey CG, Colston BW, Rothberg JM, Link DR, Leamon JH (2008) Anal Chem 80:8975–8981

    CAS  Google Scholar 

  136. Novak R, Zeng Y, Shuga J, Venugopalan G, Fletcher DA, Smith MT, Mathies RA (2011) Angew Chem Int Ed 50:390–395

    CAS  Google Scholar 

  137. Joensson HN, Svahn HA (2012) Angew Chem Int Ed Engl 51:12176–12192

    CAS  Google Scholar 

  138. Brown RB, Audet J (2008) J R Soc Interface 5:S131–S138

    CAS  Google Scholar 

  139. Di Carlo D, Jeong KH, Lee LP (2003) Lab Chip 3:287–291

    Google Scholar 

  140. Kim J, Hong JW, Kim DP, Shin JH, Park I (2012) Lab Chip 12:2914–2921

    CAS  Google Scholar 

  141. Hanahan D, Weinberg RA (2011) Cell 144:646–674

    CAS  Google Scholar 

  142. Yarden Y, Caldes C, EAfCR (2013) Eur J Cancer 49:2619–2620

    Google Scholar 

  143. Fidler IJ (2012) Hum Vaccin Immunother 8:1141–1142

    CAS  Google Scholar 

  144. Swanton C (2012) Cancer Res 72:4875–4882

    CAS  Google Scholar 

  145. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Cell 140:62–73

    CAS  Google Scholar 

  146. Verga Falzacappa MV, Ronchini C, Reavie LB, Pelicci PG (2012) FEBS J 279:3559–3572

    CAS  Google Scholar 

  147. Liu X, Long F, Peng H, Aerni SJ, Jiang M, Sánchez-Blanco A, Murray JI, Preston E, Mericle B, Batzoglou S, Myers EW, Kim SK (2009) Cell 139:623–633

    CAS  Google Scholar 

  148. Barteneva NS, Ketman K, Fasler-Kan E, Potashnikova D, Vorobjev IA (2013) Biochim Biophys Acta 1836:105–122

    CAS  Google Scholar 

  149. Munoz J, Swanton C, Kurzrock R (2013) Am Soc Clin Oncol Educ Book 2013:127–134

    Google Scholar 

  150. André F, Ciccolini J, Spano JP, Penault-Llorca F, Mounier N, Freyer G, Blay JY, Milano G (2013) Pharmacogenomics 14:931–939

    Google Scholar 

  151. Dean M, Fojo T, Bates S (2005) Nat Rev Cancer 5:275–284

    CAS  Google Scholar 

  152. Onstenk W, Gratama JW, Foekens JA, Sleijfer S (2013) Cancer Treat Rev 39:691–700

    CAS  Google Scholar 

  153. Sieuwerts AM, Jeffrey SS (2012) Recent Results Cancer Res 195:125–140

    Google Scholar 

  154. de Castro Gonzalez D, Clarke PA, Al-Lazikani B, Workman P (2013) Clin Pharmacol Ther 93:252–259

    Google Scholar 

  155. Heng HHQ, Stevens JB, Bremer SW, Liu G, Abdallah BY, Ye CJ (2011) Adv Cancer Res 112:217–253

    CAS  Google Scholar 

  156. Martini M, Vecchione L, Siena S, Tejpar S, Bardelli A (2012) Nat Rev Clin Oncol 9:87–97

    CAS  Google Scholar 

  157. Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R (2012) Nature 483:100–103

    CAS  Google Scholar 

  158. Berns K, Bernards R (2012) Drug Resist Updat 15:268–275

    CAS  Google Scholar 

  159. Fehér LZ, Pocsay G, Krenács L, Zvara A, Bagdi E, Pocsay R, Lukács G, Győry F, Gazdag A, Tarkó E, Puskás LG (2012) Pathol Oncol Res 18:449–458

    Google Scholar 

  160. Mwenifumbo JC, Marra MA (2013) Nat Rev Genet 14:321–332

    CAS  Google Scholar 

  161. Visvader J, Lindeman G (2008) Nat Rev Cancer 8:755–768

    CAS  Google Scholar 

  162. Drewa T, Czerwinski M, Olkowska J (2011) Stem Cell Studies 1:e7

    Google Scholar 

  163. Danila DC, Pantel K, Fleisher M, Scher HI (2011) Cancer J 17:438–450

    CAS  Google Scholar 

  164. Tewes M, Aktas B, Welt A, Mueller S, Hauch S, Kimmig R, Kasimir-Bauer S (2009) Breast Cancer Res Treat 115:581–590

    Google Scholar 

  165. Miller MC, Doyle GV, Terstappen LWMM (2010) J Oncol 2010:617421

    Google Scholar 

  166. Zhao M, Schiro PG, Kuo JS, Koehler KM, Sabath DE, Popov V, Feng Q, Chiu DT (2013) Anal Chem 85:2465–2471

    CAS  Google Scholar 

  167. Wendel M, Bazhenova L, Boshuizen R, Kolatkar A, Honnatti M, Cho EH, Marrinucci D, Sandhu A, Perricone A, Thistlethwaite P, Bethel K, Nieva J, Heuvel M, Kuhn P (2012) Phys Biol 9:016005

    Google Scholar 

  168. Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM, Lax S, Waldispuehl-Geigl J, Mauermann O, Lackner C, Höfler G, Eisner F, Sill H, Samonigg H, Pantel K, Riethdorf S, Bauernhofer T, Geigl JB, Speicher MR (2013) Cancer Res 73:2965–2975

    CAS  Google Scholar 

  169. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Nature 472:90–94

    CAS  Google Scholar 

  170. Möhlendick B, Bartenhagen C, Behrens B, Honisch E, Raba K, Knoefel WT, Stoecklein NH (2013) PLoS One 8:e67031

    Google Scholar 

  171. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ, Kulp AN, Qian D, Lam JS, Ailles LE, Wong M, Joshua B, Kaplan MJ, Wapnir I, Dirbas FM, Somlo G, Garberoglio C, Paz B, Shen J, Lau SK, Quake SR, Brown JM, Weissman IL, Clarke MF (2009) Nature 458:780–783

    CAS  Google Scholar 

  172. Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, Sim S, Okamoto J, Johnston DM, Qian D, Zabala M, Bueno J, Neff NF, Wang J, Shelton AA, Visser B, Hisamori S, Shimono Y, van de Wetering M, Clevers H, Clarke MF, Quake SR (2011) Nat Biotechnol 29:1120–1127

    CAS  Google Scholar 

  173. Ramsköld D, Luo S, Wang YC, Li R, Deng Q, Faridani OR, Daniels GA, Khrebtukova I, Loring JF, Laurent LC, Schroth GP, Sandberg R (2012) Nat Biotechnol 30:777–782

    Google Scholar 

  174. Welty CJ, Coleman I, Coleman R, Lakely B, Xia J, Chen S, Gulati R, Larson SR, Lange PH, Montgomery B, Nelson PS, Vessella RL, Morrissey C (2013) BMC Mol Biol 14:6

    CAS  Google Scholar 

  175. Gasch C, Bauernhofer T, Pichler M, Langer-Freitag S, Reeh M, Seifert AM, Mauermann O, Izbicki JR, Pantel K, Riethdorf S (2013) Clin Chem 59:252–260

    CAS  Google Scholar 

  176. Ståhlberg A, Thomsen C, Ruff D, Åman P (2012) Clin Chem 58:1682–1691

    Google Scholar 

  177. Tursz T, Andre F, Lazar V, Lacroix L, Soria JC (2011) Nat Rev Clin Oncol 8:177–183

    Google Scholar 

  178. Shai RM (2006) Front Biosci 11:1414–1424

    CAS  Google Scholar 

  179. Kopf E, Zharhary D (2007) Int J Biochem Cell Biol 39:1305–1317

    CAS  Google Scholar 

  180. Irish JM, Kotecha N, Nolan GP (2006) Nat Rev Cancer 6:146–155

    CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge financial support by the European Funds for Regional Development (EFRE), the government of Upper Austria, and the EU Project TargetBinder.

Author information

Authors and Affiliations

  1. Center for Advanced Bioanalysis GmbH, Gruberstraße 40-42, 4020, Linz, Austria

    Thomas Haselgrübler, Michaela Haider, Bozhi Ji, Kata Juhasz, Alois Sonnleitner, Zsolt Balogi & Jan Hesse

Authors
  1. Thomas Haselgrübler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michaela Haider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bozhi Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kata Juhasz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alois Sonnleitner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zsolt Balogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jan Hesse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Thomas Haselgrübler or Jan Hesse.

Additional information

Published in the topical collection Multiplex Platforms in Diagnostics and Bioanalytics with guest editors Günter Peine and Günther Proll.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haselgrübler, T., Haider, M., Ji, B. et al. High-throughput, multiparameter analysis of single cells. Anal Bioanal Chem 406, 3279–3296 (2014). https://doi.org/10.1007/s00216-013-7485-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-013-7485-x

Keywords

Search

Navigation