Skip to main content
SpringerLink
Log in

Generating different profiles of gradient concentrations inside a gel-filled chamber: design and simulation

  • Technical Paper
  • Published:
Microsystem Technologies Aims and scope Submit manuscript

Abstract

Spatial and temporal in vivo variations of biochemical cues affect the cellular behavior and responses in live systems. To study the biological phenomena, an appropriate environment that could facilitate generation of gradients within extracellular spaces is highly desirable. Microfluidic platforms have been widely used in cellular biology research because of their ability to mimic in vivo environments. This paper discusses the design and simulation of a microfluidic device to generate predictable profiles of various stable gradient concentrations in a hydrogel-filled chamber. Simulations have been carried out by using Coventorware for steady state, transient mode and overlapping gradients to fine-tune the design parameters. The design will have applications in three-dimensional biological cell cultures and studies.

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

  • Abhyankar VV, Toepke MW, Cortesio CL, Lokuta MA, Huttenlocher A, Beebe DJ (2008) A platform for assessing chemotactic migration within a spatiotemporally defined 3D microenvironment. Lab Chip Miniatur Chem Biol 8:1507–1515

    Article  Google Scholar 

  • Ashe HL, Briscoe J (2006) The interpretation of morphogen gradients. Development 133:385–394

    Article  Google Scholar 

  • Bhattacharjee N, Li N, Keenan TM, Folch A (2010) A neuron-benign microfluidic gradient generator for studying the response of mammalian neurons towards axon guidance factors. Integr Biol 2:669–679

    Article  Google Scholar 

  • Cimetta E, Cannizzaro C, James R, Biechele T, Moon RT, Elvassore N, Vunjak-Novakovic G (2010) Microfluidic device generating stable concentration gradients for long term cell culture: application to Wnt3a regulation of β-catenin signaling. Lab Chip Miniatur Chem Biol 10:3277–3283

    Article  Google Scholar 

  • Cooksey GA, Sip CG, Folch A (2009) A multi-purpose microfluidic perfusion system with combinatorial choice of inputs, mixtures, gradient patterns, and flow rates. Lab Chip Miniatur Chem Biol 9:417–426

    Article  Google Scholar 

  • El-Ali J, Sorger PK, Jensen KF (2006) Cells on chips. Nature 442:403–411

    Article  Google Scholar 

  • Feng X, Du W, Luo Q, Liu BF (2009) Microfluidic chip: next-generation platform for systems biology. Anal Chim Acta 650:83–97

    Article  Google Scholar 

  • Gurdon JB, Bourillot PY (2001) Morphogen gradient interpretation. Nature 413:797–803

    Article  Google Scholar 

  • Haessler U, Kalinin Y, Swartz MA, Wu M (2009) An agarose-based microfluidic platform with a gradient buffer for 3D chemotaxis studies. Biomed Microdevices 11:827–835

    Article  Google Scholar 

  • Jedrych E, Flis S, Sofinska K, Jastrzebski Z, Chudy M, Dybko A, Brzozka Z (2011) Evaluation of cytotoxic effect of 5-fluorouracil on human carcinoma cells in microfluidic system. Sensors Actuators, B: Chemi 160:1544–1551

    Article  Google Scholar 

  • Kartalov EP, Scherer A, Quake SR, Taylor CR, Anderson WF (2007) Experimentally validated quantitative linear model for the device physics of elastomeric microfluidic valves. J Appl Phy 101:064505-1–4

    Google Scholar 

  • Keenan TM, Folch A (2007) Biomolecular gradients in cell culture systems. Lab Chip Miniatur Chem Biol 8:34–57

    Article  Google Scholar 

  • Kim M, Kim T (2010) Diffusion-based and long-range concentration gradients of multiple chemicals for bacterial chemotaxis assays. Anal Chem 82:9401–9409

    Article  Google Scholar 

  • Kim D, Lokuta MA, Huttenlocher A, Beebe DJ (2009a) Selective and tunable gradient device for cell culture and chemotaxis study. Lab Chip Miniatur Chem Biol 9:1797–1800

    Article  Google Scholar 

  • Kim T, Pinelis M, Maharbiz MM (2009b) Generating steep, shear-free gradients of small molecules for cell culture. Biomed Microdevices 11:65–73

    Article  Google Scholar 

  • Kim S, Kim HJ, Jeon NL (2010) Biological applications of microfluidic gradient devices. Integr Biol 2:584–603

    Article  MathSciNet  Google Scholar 

  • Kothapalli CR, Van Veen E, De Valence S, Chung S, Zervantonakis IK, Gertler FB, Kamm RD (2011) A high-throughput microfluidic assay to study neurite response to growth factor gradients. Lab Chip Miniatur Chem Biol 11:497–507

    Article  Google Scholar 

  • Lebrun L, Junter GA (1993) Diffusion of sucrose and dextran through agar gel membranes. Enzyme Microbial Technol 15:1057–1062

    Article  Google Scholar 

  • Li GN, Liu J, Hoffman-Kim D (2008) Multi-molecular gradients of permissive and inhibitory cues direct neurite outgrowth. Ann Biomed Eng 36:889–904

    Article  Google Scholar 

  • Melin J, Quake SR (2007) Microfluidic Large-Scale Integration: the Evolution of Design Rules for Biological Automation. Ann Biophy Biomol Struct 36:213–231

    Article  Google Scholar 

  • Millet LJ, Stewart ME, Nuzzo RG, Gillette MU (2010) Guiding neuron development with planar surface gradients of substrate cues deposited using microfluidic devices. Lab Chip Miniatur Chem Biol 10:1525–1535

    Article  Google Scholar 

  • Mosadegh B, Huango C, Park JW, Shin HS, Chung BG, Hwang SK, Lee KH, Kim HJ, Brody J, Jeon NL (2007) Generation of stable complex gradients across two-dimensional surfaces and three-dimensional gels. Langmuir 23:10910–10912

    Article  Google Scholar 

  • Park JY, Yoo SJ, Hwang CM, Lee SH (2009a) Simultaneous generation of chemical concentration and mechanical shear stress gradients using microfluidic osmotic flow comparable to interstitial flow. Lab Chip Miniatur Chem Biol 9:2194–2202

    Article  Google Scholar 

  • Park JY, Kim SK, Woo DH, Lee EJ, Kim JH, Lee SH (2009b) Differentiation of neural progenitor cells in a microfluidic chip-generated cytokine gradient. Stem Cells 27:2646–2654

    Article  Google Scholar 

  • Ruan J, Wang L, Xu M, Cui D, Zhou X, Liu D (2009) Fabrication of a microfluidic chip containing dam, weirs and gradient generator for studying cellular response to chemical modulation. Mater Sci Eng C 29:674–679

    Article  Google Scholar 

  • Saadi W, Rhee SW, Lin F, Vahidi B, Chung BG, Jeon NL (2007) Generation of stable concentration gradients in 2D and 3D environments using a microfluidic ladder chamber. Biomed Microdevices 9:627–635

    Article  Google Scholar 

  • Shin Y, Jeon JS, Han S, Jung GS, Shin S, Lee SH, Sudo R, Kamm RD, Chung S (2011) In vitro 3D collective sprouting angiogenesis under orchestrated ANG-1 and VEGF gradients. Lab Chip Miniatur Chem Biol 11:2175–2181

    Article  Google Scholar 

  • Sip CG, Bhattacharjee N, Folch A (2011) A modular cell culture device for generating arrays of gradients using stacked microfluidic flows. Biomicrofluidics 5:022210-1–9

    Google Scholar 

  • Squires TM, Quake SR (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77:977–1026

    Article  Google Scholar 

  • Steffen Hardt FS (2007) Microfluidic technologies for miniaturized analysis systems. Springer, New York

    Book  Google Scholar 

  • Stone HA, Kim S (2001) Microfluidics: basic issues, applications, and challenges. AIChE J 47:1250–1254

    Article  Google Scholar 

  • Tan DCW, Yung LYL, Roy P (2010) Controlled microscale diffusion gradients in quiescent extracellular fluid. Biomed Microdevices 12:523–532

    Article  Google Scholar 

  • Tehrani-Rokh M, Kouzani AZ, Kanwar JR (2012) Gradient Generating Microfluidic Devices for Cell Cultivation. Procedia Eng 29:1740–1744

    Article  Google Scholar 

  • Wang CJ, Li X, Lin B, Shim S, Ming GL, Levchenko A (2008a) A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues. Lab Chip Miniatur Chem Biol 8:227–237

    Article  Google Scholar 

  • Wang L, Liu D, Wang B, Sun J, Li L (2008b) Design of parallel microfluidic gradient-generating networks for studying cellular response to chemical stimuli. Front Chem China 3:384–390

    Article  Google Scholar 

  • Whitesides GM (2006) The origins and the future of microfluidics. Nature 442:368–373

    Article  Google Scholar 

  • Wu H, Huang B, Zare RN (2006) Generation of complex, static solution gradients in microfluidic channels. J Am Chem Soc 128:4194–4195

    Article  Google Scholar 

  • Yang CG, Wu YF, Xu ZR, Wang JH (2011) A radial microfluidic concentration gradient generator with high-density channels for cell apoptosis assay. Lab Chip Miniatur Chem Biol 11:3305–3312

    Article  Google Scholar 

  • Young EWK, Simmons CA (2010) Macro-and microscale fluid flow systems for endothelial cell biology. Lab Chip Miniatur Chem Biol 10:143–160

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Engineering, Deakin University, Geelong, VIC, 3216, Australia

    Masoomeh Tehranirokh & Abbas Z. Kouzani

  2. School of Life and Environmental Sciences, Deakin University, Geelong, VIC, 3216, Australia

    Paul S. Francis

  3. Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Institute for Frontier Materials (IFM), Deakin University, Geelong, VIC, 3216, Australia

    Jagat R. Kanwar

Authors
  1. Masoomeh Tehranirokh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abbas Z. Kouzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul S. Francis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jagat R. Kanwar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masoomeh Tehranirokh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tehranirokh, M., Kouzani, A.Z., Francis, P.S. et al. Generating different profiles of gradient concentrations inside a gel-filled chamber: design and simulation. Microsyst Technol 19, 623–628 (2013). https://doi.org/10.1007/s00542-012-1673-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00542-012-1673-z

Keywords

Search

Navigation