Abstract
Microfluidic technology has made a significant impact in neurobiological research. The new capabilities offered by microfluidic devices allow researchers to investigate neurobiological phenomena in ways previously unachievable using traditional cell biology techniques. Here we detail the fabrication of a microfluidic cell coculture platform that uses pneumatically or hydraulically controlled valves to reversibly separate cell populations. Using this platform, communication between cell populations in different culture chambers can be enabled or restricted as desired. This allows for both growth of different cell types in each respective optimal culture media and separate treatment of individual cell populations with transfecting agents, growth factors, and drugs, etc. At a desired time-point, cell-cell interactions can be studied by deactivating the valve. The device has been used previously to transfect neurons with different fluorescent presynaptic and postsynaptic markers and then observe in real-time the subsequent process of synapse formation. Additionally, the platform has been an effective tool for investigating the role of glia–neuron communication on synaptic formation and stability. In this chapter, the design, fabrication, and operation of the valve-enabled microfluidic cell coculture platform are clearly described so as to enable the reader to replicate the device for use in future neurobiological research.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Taylor AM, Jeon NL (2010) Micro-scale and microfluidic devices for neurobiology. Curr Opin Neurobiol 20:640–647
Meyvantsson I, Beebe DJ (2008) Cell culture models in microfluidic systems. Annu Rev Anal Chem (Palo Alto Calif) 1:423–449
Gross PG, Kartalov EP, Scherer A, Weiner LP (2007) Applications of microfluidics for neuronal studies. J Neurol Sci 252(2):135–143
Park JW, Kim HJ, Kang MW, Jeon NL (2013) Advances in microfluidics-based experimental methods for neuroscience research. Lab Chip 13(4):509–521
Biffi E, Piraino F, Pedrocchi A, Fiore GB, Ferrigno G, Redaelli A, Menegon A, Rasponi M (2012) A microfluidic platform for controlled biochemical stimulation of twin neuronal networks. Biomicrofluidics 6(2):24106–2410610
Chung BG, Flanagan LA, Rhee SW, Schwartz PH, Lee AP, Monuki ES, Jeon NL (2005) Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab Chip 5(4):401–406
Taylor A, Blurton-Jones M, Rhee S, Cribbs DH, Cotman CW, Jeon NL (2005) A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods 2(8):599–605
Zhou J, Yan H, Ren K, Dai W, Wu H (2009) Convenient method for modifying poly(dimethylsiloxane) with poly(ethylene glycol) in microfluidics. Anal Chem 81(16):6627–6632
Duffy DC, McDonald JC, Schueller OJ, Whitesides GM (1998) Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal Chem 70(23):4974–4984
Mukhopadhyay R (2007) When PDMS isn’t the best. What are its weaknesses, and which other polymers can researchers add to their toolboxes? Anal Chem 79(9):3248–3253
Toepke MW, Beebe DJ (2006) PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6(12):1484–1486
El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442(7101):403–411
McDonald JC, Whitesides GM (2002) Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 35(7):491–499
Zhang M, Wu J, Wang L, Xiao K, Wen W (2010) A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips. Lab Chip 10(9):1199–1203
Unger MA, Chou H-P, Thorsen T, Scherer A, Quake SR (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288(5463):113–116
Brantley-Sieders DM, Dunaway CM, Rao M, Short S, Hwang Y, Gao Y, Li D, Jiang A, Shyr Y, Wu JY, Chen J (2011) Angiocrine factors modulate tumor proliferation and motility through EphA2 repression of Slit2 tumor suppressor function in endothelium. Cancer Res 71(3):976–987
Gao Y, Majumdar D, Jovanovic B, Shaifer C, Lin PC, Zijlstra A, Webb DJ, Li D (2011) A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology. Biomed Microdevices 13(3):539–548
Majumdar D, Gao Y, Li D, Webb DJ (2011) Co-culture of neurons and glia in a novel microfluidic platform. J Neurosci Methods 196(1):38–44
Shi M, Majumdar D, Gao Y, Brewer B, Goodwin C, McLean JA, Li D, Webb DJ (2013) Glia co-culture with neurons in microfluidic platforms promotes the formation and stabilization of synaptic contacts. Lab Chip 13(15):3008–3021
Lynn NS, Dandy DS (2009) Passive microfluidic pumping using coupled capillary/evaporation effects. Lab Chip 9(23):3422–3429
Walker GM, Beebe DJ (2002) An evaporation-based microfluidic sample concentration method. Lab Chip 2(2):57–61
Bodas D, Khan-Malek C (2007) Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment—an SEM investigation. Sensors Actuator B Chem 123(1):368–373
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Brewer, B.M., Webb, D.J., Li, D. (2015). The Fabrication of Microfluidic Platforms with Pneumatically/Hydraulically Controlled PDMS Valves and Their Use in Neurobiological Research. In: Biffi, E. (eds) Microfluidic and Compartmentalized Platforms for Neurobiological Research. Neuromethods, vol 103. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2510-0_1
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2510-0_1
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2509-4
Online ISBN: 978-1-4939-2510-0
eBook Packages: Springer Protocols