Abstract
Microfluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fluidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special coculture models that are highly concerned in a different spatial and temporal way.
Similar content being viewed by others
References
Whitesides GM. The origins and the future of microfluidics. Nature, 2006, 442(7101): 368–373
Haeberle S, Zengerle R. Microfluidic platforms for lab-on-a-chip applications. Lab on a Chip, 2007, 7(9): 1094–1110
Han K N, Li C A, Seong G H. Microfluidic chips for immunoassays. Annual Review of Analytical Chemistry (Palo Alto, Calif.), 2013, 6(1): 119–141
Nan L, Jiang Z, Wei X. Emerging microfluidic devices for cell lysis: A review. Lab on a Chip, 2014, 14(6): 1060–1073
Smejkal P, Bottenus D, Breadmore M C, Guijt R M, Ivory C F, Foret F, Macka M. Microfluidic isotachophoresis: A review. Electrophoresis, 2013, 34(11): 1493–1509
Ma S, Loufakis D N, Cao Z, Chang Y, Achenie L, Lu C. Diffusionbased microfluidic PCR for “one-pot” analysis of cells. Lab on a Chip, 2014, 14(16): 2905–2909
Sommer G J, Hatch A V, Singh A K, Wang Y C. Microfluidic device having an immobilized pH gradient and page gels for protein separation and analysis: US Patent 8728290, 2014-5-20
Jebrail M J, Renzi R F, Sinha A, Van De Vreugde J, Gondhalekar C, Ambriz C, Meagher R J, Branda S S. A solvent replenishment solution for managing evaporation of biochemical reactions in airmatrix digital microfluidics devices. Lab on a Chip, 2015, 15(1): 151–158
Ren K, Chen Y, Wu H. New materials for microfluidics in biology. Current Opinion in Biotechnology, 2014, 25: 78–85
Sia S K, Whitesides G M. Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies. Electrophoresis, 2003, 24(21): 3563–3576
Giulitti S, Magrofuoco E, Prevedello L, Elvassore N. Optimal periodic perfusion strategy for robust long-term microfluidic cell culture. Lab on a Chip, 2013, 13(22): 4430–4441
Zhang Q, Liu T, Qin J. A microfluidic-based device for study of transendothelial invasion of tumor aggregates in realtime. Lab on a Chip, 2012, 12(16): 2837–2842
Ziolkowska K, Jedrych E, Kwapiszewski R, Lopacinska J, Skolimowski M, Chudy M. PDMS/glass microfluidic cell culture system for cytotoxicity tests and cells passage. Sensors and Actuators. B, Chemical, 2010, 145(1): 533–542
El-Ali J, Sorger P K, Jensen K F. Cells on chips. Nature, 2006, 442(7101): 403–411
Mehling M, Tay S. Microfluidic cell culture. Current Opinion in Biotechnology, 2014, 25: 95–102
Xiong B, Ren K, Shu Y, Chen Y, Shen B, Wu H. Recent developments in microfluidics for cell studies. Advanced Materials, 2014, 26(31): 5525–5532
Nge P N, Rogers C I, Woolley A T. Advances in microfluidic materials, functions, integration, and applications. Chemical Reviews, 2013, 113(4): 2550–2583
Torisawa Y S, Mosadegh B, Luker G D, Morell M, O’Shea K S, Takayama S. Microfluidic hydrodynamic cellular patterning for systematic formation of co-culture spheroids. Integrative Biology, 2009, 1(11-12): 649–654
Skafte-Pedersen P, Hemmingsen M, Sabourin D, Blaga F S, Bruus H, Dufva M. A self-contained, programmable microfluidic cell culture system with real-time microscopy access. Biomedical Microdevices, 2012, 14(2): 385–399
Wang D Y, Wu S C, Lin S P, Hsiao S H, Chung T W, Huang Y Y. Evaluation of transdifferentiation from mesenchymal stem cells to neuron-like cells using microfluidic patterned co-culture system. Biomedical Microdevices, 2011, 13(3): 517–526
Wei C W, Cheng J Y, Young T H. Elucidating In vitro cell-cell interaction using a microfluidic coculture system. Biomedical Microdevices, 2006, 8(1): 65–71
Kobel S, Valero A, Latt J, Renaud P, Lutolf M. Optimization of microfluidic single cell trapping for long-term on-chip culture. Lab on a Chip, 2010, 10(7): 857–863
Mazutis L, Gilbert J, Ung WL, Weitz D A, Griffiths A D, Heyman J A. Single-cell analysis and sorting using droplet-based microfluidics. Nature Protocols, 2013, 8(5): 870–891
Yin H, Marshall D. Microfluidics for single cell analysis. Current Opinion in Biotechnology, 2012, 23(1): 110–119
Kim L, Toh Y C, Voldman J, Yu H. A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab on a Chip, 2007, 7(6): 681–694
Huang C P, Lu J, Seon H, Lee A P, Flanagan L A, Kim H Y, Putnam A J, Jeon N L. Engineering microscale cellular niches for threedimensional multicellular co-cultures. Lab on a Chip, 2009, 9(12): 1740–1748
Liu T, Lin B, Qin J. Carcinoma-associated fibroblasts promoted tumor spheroid invasion on a microfluidic 3D co-culture device. Lab on a Chip, 2010, 10(13): 1671–1677
Zhou M, Ma H, Lin H, Qin J. Induction of epithelial-tomesenchymal transition in proximal tubular epithelial cells on microfluidic devices. Biomaterials, 2014, 35(5): 1390–1401
Unger M A, Chou H P, Thorsen T, Scherer A, Quake S R. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science, 2000, 288(5463): 113–116
Liu A, Liu W, Wang Y, Wang J C, Tu Q, Liu R, Xu J, Shen S, Wang J. Microvalve and liquid membrane double-controlled integrated microfluidics for observing the interaction of breast cancer cells. Microfluidics and Nanofluidics, 2012, 14(3-4): 515–526
Majumdar D, Gao Y, Li D, Webb D J. Co-culture of neurons and glia in a novel microfluidic platform. Journal of Neuroscience Methods, 2011, 196(1): 38–44
Gao Y, Majumdar D, Jovanovic B, Shaifer C, Lin P C, Zijlstra A, Webb D J, Li D. A versatile valve-enabled microfluidic cell coculture platform and demonstration of its applications to neurobiology and cancer biology. Biomedical Microdevices, 2011, 13(3): 539–548
Liu W, Li L, Wang X, Ren L, Wang X, Wang J, Tu Q, Huang X, Wang J. An integrated microfluidic system for studying cellmicroenvironmental interactions versatilely and dynamically. Lab on a Chip, 2010, 10(13): 1717–1724
Zheng C, Zhao L, Chen G, Zhou Y, Pang Y, Huang Y. Quantitative study of the dynamic tumor-endothelial cell interactions through an integrated microfluidic coculture system. Analytical Chemistry, 2012, 84(4): 2088–2093
Brewer B M, Shi M, Edd J F, Webb D J, Li D. A microfluidic cell co-culture platform with a liquid fluorocarbon separator. Biomedical Microdevices, 2014, 16: 311–323
Yeon J H, Ryu H R, Chung M, Hu Q P, Jeon N L. In vitro formation and characterization of a perfusable three-dimensional tubular capillary network in microfluidic devices. Lab on a Chip, 2012, 12(16): 2815–2822
Businaro L, De Ninno A, Schiavoni G, Lucarini V, Ciasca G, Gerardino A, Belardelli F, Gabriele L, Mattei F. Cross talk between cancer and immune cells: Exploring complex dynamics in a microfluidic environment. Lab on a Chip, 2013, 13(2): 229–239
Huang Y, Agrawal B, Clark P A, Williams J C, Kuo J S. Evaluation of cancer stem cell migration using compartmentalizing microfluidic devices and live cell imaging. Journal of Visualized Experiments, 2011, 58: 3297
De Jong J, Lammertink R G, Wessling M. Membranes and microfluidics: A review. Lab on a Chip, 2006, 6(9): 1125–1139
Chen Q, Wu J, Zhuang Q, Lin X, Zhang J, Lin J M. Microfluidic isolation of highly pure embryonic stem cells using feeder-separated co-culture system. Scientific Reports, 2013, 3: 1–6
Sip C G, Bhattacharjee N, Folch A. Microfluidic transwell inserts for generation of tissue culture-friendly gradients in well plates. Lab on a Chip, 2014, 14(2): 302–314
Ostrovidov S, Sakai Y, Fujii T. Integration of a pump and an electrical sensor into a membrane-based PDMS microbioreactor for cell culture and drug testing. Biomedical Microdevices, 2011, 13(5): 847–864
Van Dersarl J J, Xu A M, Melosh N A. Rapid spatial and temporal controlled signal delivery over large cell culture areas. Lab on a Chip, 2011, 11(18): 3057–3063
Jang K J, Suh K Y. A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab on a Chip, 2010, 10(1): 36–42
Ramadan Q, Jafarpoorchekab H, Huang C, Silacci P, Carrara S, Koklu G, Ghaye J, Ramsden J, Ruffert C, Vergeres G, Gijs M A. NutriChip: Nutrition analysis meets microfluidics. Lab on a Chip, 2013, 13(2): 196–203
Miura S, Morimoto Y, Takeuchi S. Multi-layered placental barrier structure integrated with microfluidic channels. 2013 IEEE 26th International Conference. IEEE, 2013: 257–258
Lee Y. Sudo R, Komatsu T, Miki N, Mitaka T, Ikeda M, Tanishita K. Pattern microfluidic hydrostatic deposition patterning for a confined hepatocyte-biliary epithelial cell co-culture system. 2011 International Symposium. IEEE, 2011: 10–15
Chin L K, Luo K Q, Park W. Double-layer hepatocyte tumor coculture using hydrogel for drug affectivity and specificity analysis. 2012 IEEE 25th International Conference. IEEE, 2012: 808–811
Liu Z, Shum H C. Fabrication of uniform multi-compartment particles using microfludic electrospray technology for cell coculture studies. Biomicrofluidics, 2013, 7(4): 044117
Shi M, Majumdar D, Gao Y, Brewer B M, Goodwin C R, McLean J A, Li D, Webb D J. Glia co-culture with neurons in microfluidic platforms promotes the formation and stabilization of synaptic contacts. Lab on a Chip, 2013, 13(15): 3008–3021
Sudo R, Chung S, Zervantonakis I K, Vickerman V, Toshimitsu Y, Griffith L G, Kamm R D. Transport-mediated angiogenesis in 3D epithelial coculture. FASEB Journal, 2009, 23(7): 2155–2164
Purtscher M, Rothbauer M, Holnthoner W, Redl H, Ertl P. Establishment of Vascular Networks in Biochips Using Co-cultures of Adipose Derived Stem Cells and Endothelial Cells in a 3D Fibrin Matrix. 6th European Conference of the International Federation for Medical and Biological Engineering. Springer International Publishing, 2015: 313–317
Chen M B, Srigunapalan S, Wheeler A R, Simmons C A. A 3D microfluidic platform incorporating methacrylated gelatin hydrogels to study physiological cardiovascular cell-cell interactions. Lab on a Chip, 2013, 13(13): 2591–2598
Chung S, Sudo R, Mack P J, Wan C R, Vickerman V, Kamm R D. Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab on a Chip, 2009, 9(2): 269–275
Ioannis K, Zervantonakis S K H A, Joseph L, Charestd J L. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(34): 13151–13520
Xie Y, Zhang W, Wang L, Sun K, Sun Y, Jiang X. A microchipbased model wound with multiple types of cells. Lab on a Chip, 2011, 11(17): 2819–2822
Ricci C, Moroni L, Danti S. Cancer tissue engineering-new perspectives in understanding the biology of solid tumours-a critical review. OA Tissue Engineering, 2013, 1(1): 4
Ma H, Liu T, Qin J, Lin B. Characterization of the interaction between fibroblasts and tumor cells on a microfluidic co-culture device. Electrophoresis, 2010, 31(10): 1599–1605
Hockemeyer K, Janetopoulos C, Terekhov A, Hofmeister W, Vilgelm A, Costa L, Wikswo J, Richmond A. Engineered threedimensional microfluidic device for interrogating cell-cell interactions in the tumor microenvironment. Biomicrofluidics, 2014, 8(4): 044105
Ye N, Qin J, Shi W, Liu X, Lin B. Cell-based high content screening using an integrated microfluidic device. Lab on a Chip, 2007, 7(12): 1696–1704
Yang Y, Yang X, Zou J, Jia C, Hu Y, Du H, Wang H. Evaluation of photodynamic therapy efficiency using an In vitro three-dimensional microfluidic breast cancer tissue model. Lab on a Chip, 2015, 15(3): 735–744
Agliari E, Biselli E, De Ninno A, Schiavoni G, Gabriele L, Gerardino A, Mattei F, Barra A, Businaro L. Cancer-driven dynamics of immune cells in a microfluidic environment. Scientific Reports, 2014, 4: 1–15
Hsu T H, Kao Y L, Lin WL, Xiao J L, Kuo P L, Wu C W, Liao WY, Lee C H. The migration speed of cancer cells influenced by macrophages and myofibroblasts co-cultured in a microfluidic chip. Integrative Biology, 2012, 4(2): 177–182
Park J Y, Kim H O, Kim K D, Kim S K, Lee S K, Jung H. Monitoring the status of T-cell activation in a microfluidic system. Analyst (London), 2011, 136(13): 2831–2836
Charwat V, Rothbauer M, Tedde S F, Hayden O, Bosch J J, Muellner P, Hainberger R, Ertl P. Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip. Analytical Chemistry, 2013, 85(23): 11471–11478
Muoz-Pinedo C, Green D R, van den Berg C A. Confocal restricted-height imaging of suspension cells (CRISC) in a PDMS microdevice during apoptosis. Lab on a Chip, 2005, 5(6): 628–633
Li P, Stratton Z S, Dao M, Ritz J, Huang T J. Probing circulating tumor cells in microfluidics. Lab on a Chip, 2013, 13(4): 602–609
Millet L J, Stewart M E, Sweedler J V, Nuzzo R G, Gillette M U. Microfluidic devices for culturing primary mammalian neurons at low densities. Lab on a Chip, 2007, 7(8): 987–994
Millet L J, Stewart M E, Nuzzo R G, Gillette M U. Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab on a Chip, 2010, 10(12): 1525–1535
Wang J, Ren L, Li L, Liu W, Zhou J, Yu W, Tong D, Chen S. Microfluidics: A new cosset for neurobiology. Lab on a Chip, 2009, 9(5): 644–652
Millet L J, Gillette MU. New perspectives on neuronal development via microfluidic environments. Trends in Neurosciences, 2012, 35(12): 752–761
Dinh N D, Chiang Y Y, Hardelauf H, Baumann J, Jackson E, Waide S, Sisnaiske J, Frimat J P, van Thriel C, Janasek D, Peyrin JM, West J. Microfluidic construction of minimalistic neuronal co-cultures. Lab on a Chip, 2013, 13(7): 1402–1412
Park J, Koito H, Li J, Han A. Microfluidic compartmentalized coculture platform for CNS axon myelination research. Biomedical Microdevices, 2009, 11(6): 1145–1153
Peyrin J M, Deleglise B, Saias L, Vignes M, Gougis P, Magnifico S, Betuing S, Pietri M, Caboche J, Vanhoutte P, Viovy J L, Brugg B. Axon diodes for the reconstruction of oriented neuronal networks in microfluidic chambers. Lab on a Chip, 2011, 11(21): 3663–3673
Kunze A, Lengacher S, Dirren E, Aebischer P, Magistretti P J, Renaud P. Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS. Integrative Biology, 2013, 5(7): 964–975
Southam K A, King A E, Blizzard C A, McCormack G H, Dickson T C. Microfluidic primary culture model of the lower motor neuronneuromuscular junction circuit. Journal of Neuroscience Methods, 2013, 218(2): 164–169
Kim H J, Huh D, Hamilton G, Ingber D E. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsislike motions and flow. Lab on a Chip, 2012, 12(12): 2165–2174
Kim J, Hegde M, Jayaraman A. Co-culture of epithelial cells and bacteria for investigating host-pathogen interactions. Lab on a Chip, 2010, 10(1): 43–50
Hong JW, Song S, Shin J H. A novel microfluidic co-culture system for investigation of bacterial cancer targeting. Lab on a Chip, 2013, 13(15): 3033–3040
Huh D, Hamilton G A, Ingber D E. From 3D cell culture to organson-chips. Trends in Cell Biology, 2011, 21(12): 745–754
Kostadinova R, Boess F, Applegate D, Suter L, Weiser T, Singer T, Naughton B, Roth A. A long-term three dimensional liver co-culture system for improved prediction of clinically relevant drug-induced hepatotoxicity. Toxicology and Applied Pharmacology, 2013, 268(1): 1–16
Lee S A, No D Y, Kang E, Ju J, Kim D S, Lee S H. Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte–hepatic stellate cell interactions and flow effects. Lab on a Chip, 2013, 13(18): 3529–3537
Jang K J, Cho H S, Kang D H, Bae W G, Kwon T H, Suh K Y. Fluid-shear-stress-induced translocation of aquaporin-2 and reorganization of actin cytoskeleton in renal tubular epithelial cells. Integrative Biology, 2011, 3(2): 134–141
Huh D, Fujioka H, Tung Y C, Futai N, Paine R, Grotberg J B, Takayama S. Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(48): 18886–18891
Huh D, Matthews B D, Mammoto A, Montoya-Zavala M, Hsin H Y, Ingber D E. Reconstituting organ-level lung functions on a chip. Science, 2010, 328(5986): 1662–1668
Sung J H, Esch M B, Prot J M, Long C J, Smith A, Hickman J J, Shuler M L. Microfabricated mammalian organ systems and their integration into models of whole animals and humans. Lab on a Chip, 2013, 13(7): 1201–1212
Chan C Y, Huang P H, Guo F, Ding X, Kapur V, Mai J D, Yuen P K, Huang T J. Accelerating drug discovery via organs-on-chips. Lab on a Chip, 2013, 13(24): 4697–4710
Choucha-Snouber L, Aninat C, Grsicom L, Madalinski G, Brochot C, Poleni P E, Razan F, Guillouzo C G, Legallais C, Corlu A, Leclerc E. Investigation of ifosfamide nephrotoxicity induced in a liver-kidney co-culture biochip. Biotechnology and Bioengineering, 2013, 110(2): 597–608
Novik E, Maguire T J, Chao P, Cheng K, Yarmush M L. A microfluidic hepatic coculture platform for cell-based drug metabolism studies. Biochemical Pharmacology, 2010, 79(7): 1036–1044
Torisawa Y S, Spina C S, Mammoto T, Mammoto A, Weaver J C, Tat T, Collins J J, Ingber D E. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nature Methods, 2014, 11(6): 663–669
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, R., Lv, X., Zhang, X. et al. Microfluidics for cell-cell interactions: A review. Front. Chem. Sci. Eng. 10, 90–98 (2016). https://doi.org/10.1007/s11705-015-1550-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11705-015-1550-2