Skip to main content
SpringerLink
Log in

Cell Microarrays for Biomedical Applications

  • Protocol
Microarray Technology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1368))

Abstract

In this chapter the state of the art of live cell microarrays for high-throughput biological assays are reviewed. The fabrication of novel microarrays with respect to material science and cell patterning methods is included. A main focus of the chapter is on various aspects of the application of cell microarrays by providing selected examples in research fields such as biomaterials, stem cell biology and neuroscience. Additionally, the importance of microfluidic technologies for high-throughput on-chip live-cell microarrays is highlighted for single-cell and multi-cell assays as well as for 3D tissue constructs.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
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 119.99
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. Fernandes TG, Diogo MM, Clark DS, Dordick JS, Cabral JMS (2009) High-throughput cellular microarray platforms: applications in drug discovery, toxicology and stem cell research. Trends Biotechnol 27:342–349

    Article  CAS  PubMed  Google Scholar 

  2. Angres B (2005) Cell microarrays. Expert Rev Mol Diagn 5:769–779

    Article  CAS  PubMed  Google Scholar 

  3. Ziauddin J, Sabatini DM (2001) Microarrays of cells expressing defined cDNAs. Nature 411:107–110

    Article  CAS  PubMed  Google Scholar 

  4. West J, Becker M, Tombrink S, Manz A (2008) Micro total analysis systems: latest achievements. Anal Chem 80:4403–4419

    Article  CAS  PubMed  Google Scholar 

  5. Dittrich PS, Manz A (2006) Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov 5:210–218

    Article  CAS  PubMed  Google Scholar 

  6. Richter L, Charwat V, Jungreuthmayer C, Bellutti F, Brueckl H, Ertl P (2011) Monitoring cellular stress responses to nanoparticles using a lab-on-a-chip. Lab Chip 11:2551–2560

    Article  CAS  PubMed  Google Scholar 

  7. Charwat V, Rothbauer M, Tedde SF, Hayden O, Bosch JJ, Muellner P, Hainberger R, Ertl P (2013) Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip. Anal Chem 85:11471–11478

    Article  CAS  PubMed  Google Scholar 

  8. Novak R, Wartmann D, Mathies RA, Dostálek J, Ertl P (2015) Microfluidic platform for multiplexed cell sampling and time-resolved spr-based cytokine sensing. In: Lacković I, Vasic D (eds.) 6th European conference of the international federation for medical and biological engineering—MBEC 2014, 7–11 September 2014, Dubrovnik, Croatia, Springer. pp. 785–788

    Google Scholar 

  9. Ertl P, Sticker D, Charwat V, Kasper C, Lepperdinger G (2014) Lab-on-a-chip technologies for stem cell analysis. Trends Biotechnol 32:245–253

    Article  CAS  PubMed  Google Scholar 

  10. Ito Y, Nogawa M, Takeda M, Shibuya T (2005) Photo-reactive polyvinylalcohol for photo-immobilized microarray. Biomaterials 26:211–216

    Article  CAS  PubMed  Google Scholar 

  11. Falsey JR, Renil M, Park S, Li S, Lam KS (2001) Peptide and small molecule microarray for high throughput cell adhesion and functional assays. Bioconjug Chem 12:346–353

    Article  CAS  PubMed  Google Scholar 

  12. Xu QC, Miyamoto S, Lam KS (2004) A novel approach to chemical microarray using ketone-modified macromolecular scaffolds: application in micro cell-adhesion assay. Mol Divers 8:301–310

    Article  CAS  PubMed  Google Scholar 

  13. Soen Y, Chen DS, Kraft DL, Davis MM, Brown PO (2003) Detection and characterization of cellular immune responses using peptide-MHC microarrays. PLoS Biol 1:E65

    Article  PubMed Central  PubMed  Google Scholar 

  14. Stone JD, Demkowicz WE Jr, Stern LJ (2005) HLA-restricted epitope identification and detection of functional T cell responses by using MHC-peptide and costimulatory microarrays. Proc Natl Acad Sci U S A 102:3744–3749

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Nimrichter L, Gargir A, Gortler M, Altstock RT, Shtevi A, Weisshaus O, Fire E, Dotan N, Schnaar RL (2004) Intact cell adhesion to glycan microarrays. Glycobiology 14:197–203

    Article  CAS  PubMed  Google Scholar 

  16. Hovis JS, Boxer SG (2001) Patterning and composition arrays of supported lipid bilayers by microcontact printing. Langmuir 17:3400–3405

    Article  CAS  Google Scholar 

  17. Groves JT, Mahal LK, Bertozzi CR (2001) Control of cell adhesion and growth with micropatterned supported lipid membranes. Langmuir 17:5129–5133

    Article  CAS  Google Scholar 

  18. Anderson DG, Peng W, Akinc A, Hossain N, Kohn A, Padera R, Langer R, Sawicki JA (2004) A polymer library approach to suicide gene therapy for cancer. Proc Natl Acad Sci U S A 101:16028–16033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yang J, Mei Y, Hook AL, Taylor M, Urquhart AJ, Bogatyrev SR, Langer R, Anderson DG, Davies MC, Alexander MR (2010) Polymer surface functionalities that control human embryoid body cell adhesion revealed by high throughput surface characterization of combinatorial material microarrays. Biomaterials 31:8827–8838

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Anderson DG, Levenberg S, Langer R (2004) Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol 22:863–866

    Article  CAS  PubMed  Google Scholar 

  21. Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2:119–125

    Article  CAS  PubMed  Google Scholar 

  22. Ankam S, Teo BKK, Kukumberg M, Yim EKF (2013) High throughput screening to investigate the interaction of stem cells with their extracellular microenvironment. Organogenesis 9:128–142

    Article  PubMed Central  PubMed  Google Scholar 

  23. Mei Y, Saha K, Bogatyrev SR, Yang J, Hook AL, Kalcioglu ZI, Cho SW, Mitalipova M, Pyzocha N, Rojas F, Van Vliet KJ, Davies MC, Alexander MR, Langer R, Jaenisch R, Anderson DG (2010) Combinatorial development of biomaterials for clonal growth of human pluripotent stem cells. Nat Mater 9:768–778

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Zhang R, Mjoseng HK, Hoeve MA, Bauer NG, Pells S, Besseling R, Velugotla S, Tourniaire G, Kishen REB, Tsenkina Y, Armit C, Duffy CRE, Helfen M, Edenhofer F, de Sousa PA, Bradley M (2013) A thermoresponsive and chemically defined hydrogel for long-term culture of human embryonic stem cells. Nat Commun 4(1335):1–10

    Article  Google Scholar 

  25. Cheng XH, Wang YB, Hanein Y, Bohringer KF, Ratner BD (2004) Novel cell patterning using microheater-controlled thermoresponsive plasma films. J Biomed Mater Res A 70A:159–168

    Article  CAS  Google Scholar 

  26. Hook AL, Chang CY, Yang J, Atkinson S, Langer R, Anderson DG, Davies MC, Williams P, Alexander MR (2013) Discovery of novel materials with broad resistance to bacterial attachment using combinatorial polymer microarrays. Adv Mater 25:2542–2547

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Anglin E, Davey R, Herrid M, Hope S, Kurkuri M, Pasic P, Hor M, Fenech M, Thissen H, Voelcker NH (2010) Cell microarrays for the screening of factors that allow the enrichment of bovine testicular cells. Cytometry Part A: the journal of the International Society for Analytical Cytology 77:881–889

    Article  Google Scholar 

  28. Pernagallo S, Wu M, Gallagher MP, Bradley M (2011) Colonising new frontiers-microarrays reveal biofilm modulating polymers. J Mater Chem 21:96–101

    Article  CAS  Google Scholar 

  29. Unadkat HV, Hulsman M, Cornelissen K, Papenburg BJ, Truckenmuller RK, Carpenter AE, Wessling M, Post GF, Uetz M, Reinders MJ, Stamatialis D, van Blitterswijk CA, de Boer J (2011) An algorithm-based topographical biomaterials library to instruct cell fate. Proc Natl Acad Sci U S A 108:16565–16570

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Moe AA, Suryana M, Marcy G, Lim SK, Ankam S, Goh JZ, Jin J, Teo BK, Law JB, Low HY, Goh EL, Sheetz MP, Yim EK (2012) Microarray with micro- and nano-topographies enables identification of the optimal topography for directing the differentiation of primary murine neural progenitor cells. Small 8:3050–3061

    Article  CAS  PubMed  Google Scholar 

  31. Ohnaga T, Shimada Y, Moriyama M, Kishi H, Obata T, Takata K, Okumura T, Nagata T, Muraguchi A, Tsukada K (2013) Polymeric microfluidic devices exhibiting sufficient capture of cancer cell line for isolation of circulating tumor cells. Biomed Microdevices 15:611–616

    Article  CAS  PubMed  Google Scholar 

  32. Li N, Ho CM (2008) Photolithographic patterning of organosilane monolayer for generating large area two-dimensional B lymphocyte arrays. Lab Chip 8:2105–2112

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Ellmark P, Hogerkorp CM, Ek S, Belov L, Berglund M, Rosenquist R, Christopherson RI, Borrebaeck CAK (2008) Phenotypic protein profiling of different B cell sub-populations using antibody CD-microarrays. Cancer Lett 265:98–106

    Article  CAS  PubMed  Google Scholar 

  34. Sekine K, Revzin A, Tompkins RG, Toner M (2006) Panning of multiple subsets of leukocytes on antibody-decorated poly(ethylene) glycol-coated glass slides. J Immunol Methods 313:96–109

    Article  CAS  PubMed  Google Scholar 

  35. Wu JQ, Wang B, Belov L, Chrisp J, Learmont J, Dyer WB, Zaunders J, Cunningham AL, Dwyer DE, Saksena NK (2007) Antibody microarray analysis of cell surface antigens on CD4+ and CD8+ T cells from HIV+ individuals correlates with disease stages. Retrovirology 4:83

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Gao J, Liu C, Liu D, Wang Z, Dong S (2010) Antibody microarray-based strategies for detection of bacteria by lectin-conjugated gold nanoparticle probes. Talanta 81:1816–1820

    Article  CAS  PubMed  Google Scholar 

  37. Marimon JM, Monasterio A, Ercibengoa M, Pascual J, Prieto I, Simon L, Perez-Trallero E (2010) Antibody microarray typing, a novel technique for Streptococcus pneumoniae serotyping. J Microbiol Methods 80:274–280

    Article  CAS  PubMed  Google Scholar 

  38. Niu W, Narayanaswamy R, Scouras A, Hart GT, Davies J, Ellington AD, Iyer VR, Marcotte EM (2006) Systematic profiling of cellular phenotypes with spotted cell microarrays reveals new mating pheromone response genes. Faseb J 20:A928–A928

    Google Scholar 

  39. Bochner BR, Gadzinski P, Panomitros E (2001) Phenotype MicroArrays for high-throughput phenotypic testing and assay of gene function. Genome Res 11:1246–1255

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Schwenk JM, Stoll D, Templin MF, Joos TO (2002) Cell microarrays: an emerging technology for the characterization of antibodies. Biotechniques 33:S54–S61

    Google Scholar 

  41. Chin VI, Taupin P, Sanga S, Scheel J, Gage FH, Bhatia SN (2004) Microfabricated platform for studying stem cell fates. Biotechnol Bioeng 88:399–415

    Article  CAS  PubMed  Google Scholar 

  42. Woodruff K, Fidalgo LM, Gobaa S, Lutolf MP, Maerkl SJ (2013) Live mammalian cell arrays. Nat Methods 10:550–552

    Article  CAS  PubMed  Google Scholar 

  43. Hong BJ, Sunkara V, Park JW (2005) DNA microarrays on nanoscale-controlled surface. Nucleic Acids Res 33:e106

    Article  PubMed Central  PubMed  Google Scholar 

  44. Sunkara V, Hong BJ, Park JW (2007) Sensitivity enhancement of DNA microarray on nano-scale controlled surface by using a streptavidin-fluorophore conjugate. Biosens Bioelectron 22:1532–1537

    Article  CAS  PubMed  Google Scholar 

  45. Wang WJ, Itaka K, Ohba S, Nishiyama N, Chung UI, Yamasaki Y, Kataoka K (2009) 3D spheroid culture system on micropatterned substrates for improved differentiation efficiency of multipotent mesenchymal stem cells. Biomaterials 30:2705–2715

    Article  CAS  PubMed  Google Scholar 

  46. Berdondini L, Chippalone M, van der Wal PD, Imfeld K, de Rooij NF, Koudelka-Hep M, Tedesco M, Martinoia S, van Pelt J, Le Masson G, Garenne A (2006) A microelectrode array (MEA) integrated with clustering structures for investigating in vitro neurodynamics in confined interconnected sub-populations of neurons. Sensor Actuat B-Chem 114:530–541

    Article  CAS  Google Scholar 

  47. Maccione A, Gandolfo M, Tedesco M, Nieus T, Imfeld K, Martinoia S, Berdondini L (2010) Experimental investigation on spontaneously active hippocampal cultures recorded by means of high-density MEAs: analysis of the spatial resolution effects. Frontiers in Neuroengineering 3(4):1–12

    Google Scholar 

  48. Maccione A, Garofalo M, Nieus T, Tedesco M, Berdondini L, Martinoia S (2012) Multiscale functional connectivity estimation on low-density neuronal cultures recorded by high-density CMOS Micro Electrode Arrays. J Neurosci Methods 207:161–171

    Article  PubMed  Google Scholar 

  49. Marconi E, Nieus T, Maccione A, Valente P, Simi A, Messa M, Dante S, Baldelli P, Berdondini L, Benfenati F (2012) Emergent functional properties of neuronal networks with controlled topology. PLoS One 7:e34648

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Bakkum DJ, Frey U, Radivojevic M, Russell TL, Muller J, Fiscella M, Takahashi H, Hierlemann A (2013) Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites. Nat Commun 4(2181):1–12

    Google Scholar 

  51. Xia YN, Whitesides GM (1998) Soft lithography. Angew Chem Int Ed 37:551–575

    Article  Google Scholar 

  52. Khademhosseini A, Yeh J, Jon S, Eng G, Suh KY, Burdick JA, Langer R (2004) Molded polyethylene glycol microstructures for capturing cells within microfluidic channels. Lab Chip 4:425–430

    Article  CAS  PubMed  Google Scholar 

  53. Chiu DT, Jeon NL, Huang S, Kane RS, Wargo CJ, Choi IS, Ingber DE, Whitesides GM (2000) Patterned deposition of cells and proteins onto surfaces by using three-dimensional microfluidic systems. Proc Natl Acad Sci U S A 97:2408–2413

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Khademhosseini A, Suh KY, Jon S, Eng G, Yeh J, Chen GJ, Langer R (2004) A soft lithographic approach to fabricate patterned microfluidic channels. Anal Chem 76:3675–3681

    Article  CAS  PubMed  Google Scholar 

  55. Whitesides GM, Ostuni E, Takayama S, Jiang X, Ingber DE (2001) Soft lithography in biology and biochemistry. Annu Rev Biomed Eng 3:335–373

    Article  CAS  PubMed  Google Scholar 

  56. Narsinh KH, Sun N, Sanchez-Freire V, Lee AS, Almeida P, Hu SJ, Jan T, Wilson KD, Leong D, Rosenberg J, Yao M, Robbins RC, Wu JC (2011) Single cell transcriptional profiling reveals heterogeneity of human induced pluripotent stem cells. J Clin Invest 121:1217–1221

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Kang JH, Krause S, Tobin H, Mammoto A, Kanapathipillai M, Ingber DE (2012) A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells. Lab Chip 12:2175–2181

    Article  CAS  PubMed  Google Scholar 

  58. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M (2007) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Karabacak NM, Spuhler PS, Fachin F, Lim EJ, Pai V, Ozkumur E, Martel JM, Kojic N, Smith K, Chen PI, Yang J, Hwang H, Morgan B, Trautwein J, Barber TA, Stott SL, Maheswaran S, Kapur R, Haber DA, Toner M (2014) Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protoc 9:694–710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Hur SC, Mach AJ, Di Carlo D (2011) High-throughput size-based rare cell enrichment using microscale vortices. Biomicrofluidics 5(022206):1–10

    Google Scholar 

  61. Mach AJ, Kim JH, Arshi A, Hur SC, Di Carlo D (2011) Automated cellular sample preparation using a Centrifuge-on-a-Chip. Lab Chip 11:2827–2834

    Article  CAS  PubMed  Google Scholar 

  62. Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, Sim S, Okamoto J, Johnston DM, Qian DL, Zabala M, Bueno J, Neff NF, Wang JB, Shelton AA, Visser B, Hisamori S, Shimono Y, van de Wetering M, Clevers H, Clarke MF, Quake SR (2011) Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol 29:1120–1127

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Gossett DR, Tse HTK, Lee SA, Ying Y, Lindgren AG, Yang OO, Rao JY, Clark AT, Di Carlo D (2012) Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc Natl Acad Sci U S A 109:7630–7635

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Tse HTK, Gossett DR, Moon YS, Masaeli M, Sohsman M, Ying Y, Mislick K, Adams RP, Rao JY, Di Carlo D (2013) Quantitative diagnosis of malignant pleural effusions by single-cell mechanophenotyping. Sci Transl Med 5(212):212ra163, 1–9

    Article  PubMed  Google Scholar 

  65. Wlodkowic D, Faley S, Zagnoni M, Wikswo JP, Cooper JM (2009) Microfluidic single-cell array cytometry for the analysis of tumor apoptosis. Anal Chem 81:5517–5523

    Article  CAS  PubMed  Google Scholar 

  66. Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, Stockdale FE, Quake SR, Pease RF, Mindrinos MN, Bhanot G, Dairkee SH, Davis RW, Jeffrey SS (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One 7:e33788

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Faley SL, Copland M, Wlodkowic D, Kolch W, Seale KT, Wikswo JP, Cooper JM (2009) Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab Chip 9:2659–2664

    Article  CAS  PubMed  Google Scholar 

  68. Lecault V, VanInsberghe M, Sekulovic S, Knapp DJHF, Wohrer S, Bowden W, Viel F, McLaughlin T, Jarandehei A, Miller M, Falconnet D, White AK, Kent DG, Copley MR, Taghipour F, Eaves CJ, Humphries RK, Piret JM, Hansen CL (2011) High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays. Nat Methods 8:581–586

    Article  CAS  PubMed  Google Scholar 

  69. Boedicker JQ, Li L, Kline TR, Ismagilov RF (2008) Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics. Lab Chip 8:1265–1272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Kastrup CJ, Boedicker JQ, Pomerantsev AP, Moayeri M, Bian Y, Pompano RR, Kline TR, Sylvestre P, Shen F, Leppla SH, Tang WJ, Ismagilov RF (2008) Spatial localization of bacteria controls coagulation of human blood by ‘quorum acting’. Nat Chem Biol 4:742–750

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Han Q, Bagheri N, Bradshaw EM, Hafler DA, Lauffenburger DA, Love JC (2012) Polyfunctional responses by human T cells result from sequential release of cytokines. Proc Natl Acad Sci U S A 109:1607–1612

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Yamanaka YJ, Szeto GL, Gierahn TM, Forcier TL, Benedict KF, Brefo MSN, Lauffenburger DA, Irvine DJ, Love JC (2012) Cellular barcodes for efficiently profiling single-cell secretory responses by microengraving. Anal Chem 84:10531–10536

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  73. Jin A, Ozawa T, Tajiri K, Obata T, Kondo S, Kinoshita K, Kadowaki S, Takahashi K, Sugiyama T, Kishi H, Muraguchi A (2009) A rapid and efficient single-cell manipulation method for screening antigen-specific antibody-secreting cells from human peripheral blood. Nat Med 15:1088–1092

    Article  CAS  PubMed  Google Scholar 

  74. Berdondini L, Imfeld K, Maccione A, Tedesco M, Neukom S, Koudelka-Hep M, Martinoia S (2009) Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks. Lab Chip 9:2644–2651

    Article  CAS  PubMed  Google Scholar 

  75. Park K, Jang J, Irimia D, Sturgis J, Lee J, Robinson JP, Toner M, Bashir R (2008) ‘Living cantilever arrays’ for characterization of mass of single live cells in fluids. Lab Chip 8:1034–1041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Bierwolf J, Lutgehetmann M, Feng K, Erbes J, Deichmann S, Toronyi E, Stieglitz C, Nashan B, Ma PX, Pollok JM (2011) Primary rat hepatocyte culture on 3D nanofibrous polymer scaffolds for toxicology and pharmaceutical research. Biotechnol Bioeng 108:141–150

    Article  CAS  PubMed  Google Scholar 

  77. Li J, Tao R, Wu W, Cao HC, Xin JJ, Li J, Guo J, Jiang LY, Gao CY, Demetriou AA, Farkas DL, Li LJ (2010) 3D PLGA scaffolds improve differentiation and function of bone marrow mesenchymal stem cell-derived hepatocytes. Stem Cells Dev 19:1427–1436

    Article  CAS  PubMed  Google Scholar 

  78. Salmenpera P, Kankuri E, Bizik J, Siren V, Virtanen I, Takahashi S, Leiss M, Fassler R, Vaheri A (2008) Formation and activation of fibroblast spheroids depend on fibronectin-integrin interaction. Exp Cell Res 314:3444–3452

    Article  CAS  PubMed  Google Scholar 

  79. Bao BA, Lai CP, Naus CC, Morgan JR (2012) Pannexin1 drives multicellular aggregate compaction via a signaling cascade that remodels the actin cytoskeleton. J Biol Chem 287:8407–8416

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Jukes JM, Both SK, Leusink A, Sterk LMT, Van Blitterswijk CA, De Boer J (2008) Endochondral bone tissue engineering using embryonic stem cells. Proc Natl Acad Sci U S A 105:6840–6845

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394

    Article  CAS  PubMed  Google Scholar 

  82. Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108:407–414

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Carraro A, Hsu WM, Kulig KM, Cheung WS, Miller ML, Weinberg EJ, Swart EF, Kaazempur-Mofrad M, Borenstein JT, Vacanti JP, Neville C (2008) In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices 10:795–805

    Article  PubMed  Google Scholar 

  84. Jang KJ, Cho HS, Kang do H, Bae WG, Kwon TH, Suy KY (2011) Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells. Integrative biology : quantitative biosciences from nano to macro 3:134–141

    Article  CAS  Google Scholar 

  85. Kimura H, Yamamoto T, Sakai H, Sakai Y, Fujii T (2008) An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models. Lab Chip 8:741–746

    Article  CAS  PubMed  Google Scholar 

  86. Park J, Koito H, Li J, Han A (2009) Microfluidic compartmentalized co-culture platform for CNS axon myelination research. Biomed Microdevices 11:1145–1153

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Gu A, Shively JE (2011) Angiopoietins-1 and -2 play opposing roles in endothelial sprouting of embryoid bodies in 3D culture and their receptor Tie-2 associates with the cell-cell adhesion molecule PECAM1. Exp Cell Res 317:2171–2182

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Rouwkema J, de Boer J, Van Blitterswijk CA (2006) Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct. Tissue Eng 12:2685–2693

    Article  CAS  PubMed  Google Scholar 

  89. Rivron NC, Vrij EJ, Rouwkema J, Le Gac S, van den Berg A, Truckenmuller RK, van Blitterswijk CA (2012) Tissue deformation spatially modulates VEGF signaling and angiogenesis. Proc Natl Acad Sci U S A 109:6886–6891

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Khademhosseini A, Eng G, Yeh J, Kucharczyk PA, Langer R, Vunjak-Novakovic G, Radisic M (2007) Microfluidic patterning for fabrication of contractile cardiac organoids. Biomed Microdevices 9:149–157

    Article  PubMed  Google Scholar 

  91. Fu CY, Tseng SY, Yang SM, Hsu L, Liu CH, Chang HY (2014) A microfluidic chip with a U-shaped microstructure array for multicellular spheroid formation, culturing and analysis. Biofabrication 6(1):015009. doi:10.1088/1758-5082/6/1/015009

    Article  PubMed  Google Scholar 

  92. Dong Y, Tan OL, Loessner D, Stephens C, Walpole C, Boyle GM, Parsons PG, Clements JA (2010) Kallikrein-related peptidase 7 promotes multicellular aggregation via the alpha(5)beta(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma. Cancer Res 70:2624–2633

    Article  CAS  PubMed  Google Scholar 

  93. Frey O, Misun PM, Fluri DA, Hengstler JG, Hierlemann A (2014) Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun 5:4250. doi:10.1038/ncomms5250

    Article  CAS  PubMed  Google Scholar 

  94. Torisawa YS, Takagi A, Nashimoto Y, Yasukawa T, Shiku H, Matsue T (2007) A multicellular spheroid array to and viability realize spheroid formation, culture, assay on a chip. Biomaterials 28:559–566

    Article  CAS  PubMed  Google Scholar 

  95. Hsiao AY, Torisawa YS, Tung YC, Sud S, Taichman RS, Pienta KJ, Takayama S (2009) Microfluidic system for formation of PC-3 prostate cancer co-culture spheroids. Biomaterials 30:3020–3027

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Xu Z, Gao Y, Hao Y, Li E, Wang Y, Zhang J, Wang W, Gao Z, Wang Q (2013) Application of a microfluidic chip-based 3D co-culture to test drug sensitivity for individualized treatment of lung cancer. Biomaterials 34:4109–4117

    Article  CAS  PubMed  Google Scholar 

  97. Torisawa YS, Shiku H, Yasukawa T, Nishizawa M, Matsue T (2005) Multi-channel 3-D cell culture device integrated on a silicon chip for anticancer drug sensitivity test. Biomaterials 26:2165–2172

    Article  CAS  PubMed  Google Scholar 

  98. Wagner I, Materne EM, Brincker S, Sussbier U, Fradrich C, Busek M, Sonntag F, Sakharov DA, Trushkin EV, Tonevitsky AG, Lauster R, Marx U (2013) A dynamic multi-organ-chip for long-term cultivation and substance testing proven by 3D human liver and skin tissue co-culture. Lab Chip 13:3538–3547

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. BioSensor Technologies, AIT Austrian Institute of Technology GmbH, Muthgasse 11, 1190, Vienna, Austria

    Mario Rothbauer & Peter Ertl

  2. Institute of Applied Microbiology, University of Natural Resources and Life Sciences Vienna, Muthgasse 11/2, 1190, Vienna, Austria

    Verena Charwat

Authors
  1. Mario Rothbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Verena Charwat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Ertl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Ertl .

Editor information

Editors and Affiliations

  1. Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada

    Paul C.H. Li

  2. Dept. of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada

    Abootaleb Sedighi

  3. Department of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada

    Lin Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Rothbauer, M., Charwat, V., Ertl, P. (2016). Cell Microarrays for Biomedical Applications. In: Li, P., Sedighi, A., Wang, L. (eds) Microarray Technology. Methods in Molecular Biology, vol 1368. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3136-1_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3136-1_19

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3135-4

  • Online ISBN: 978-1-4939-3136-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation