Skip to main content
Log in

Microfluidic device for the combinatorial application and maintenance of dynamically imposed diffusional gradients

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

This article reports a microfluidic device for the generation of stable, steady-state, user-defined concentration profiles for the long-term maintenance of stable diffusion gradients. The microinstrument allows both dynamic temporal and dynamic spatial control over user-defined concentrations and concentration gradients of multiple chemicals. With this device, one can create an in vitro environment capable of approximating the complex in vivo biological condition for cellular studies. In addition, the device has potential application in combinatory drug discovery, electrophoretic applications, ligand binding, etc. 3D computer simulations and analysis of arbitrary concentration profiles are presented along with experimental validation using multiple diffusing species.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Abhyankar VV, Lokuta MA, Huttenlocher A, Beebe DJ (2006) Characterization of a membrane-based gradient generator for use in cell-signaling studies. Lab Chip 6:389–393

    Article  Google Scholar 

  • Bard AJ, Faulkner LR (2001) Electrochemical methods, 2nd edn. Wiley, pp 137–156

  • 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 5:401–406

    Article  Google Scholar 

  • Dertinger SKW, Chieu DT, Jeon NL, Whitesides GM (2001) Generation of gradients having complex shapes using microfluidic networks. Anal Chem 73:1240–1246

    Article  Google Scholar 

  • Fallon MS, Howell BA, Chauhan A (2009) Importance of Taylor dispersion in pharmacokinetic and multiple indicator dilution modelling. Math Med Biol 26(4):263–296

    Google Scholar 

  • Flanagan JG (2006) Neural map specification by gradients. Curr Opin Neurobiol 16(1):59–66

    Article  Google Scholar 

  • Goodhill GJ, Urbach JS (1999) Theoretical analysis of gradient detection by growth cones. J Neurobiol 41:230–241

    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 

  • Hattori K, Sugiura S, Kanamori T (2009) Generation of arbitrary monotonic concentration profiles by a serial dilution microfluidic network composed of microchannels with a high fluidic-resistance ratio. Lab Chip 9:1763–1772

    Article  Google Scholar 

  • Jan YN, Jan LY (2003) The control of dendrite development. Neuron 40(2):229–242

    Article  Google Scholar 

  • Jeon NL, Baskaran H, Dertinger SKW, Whitesides GM, Van de Water L, Toner M (2002) Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat Biotechnol 20(8):826–830

    Google Scholar 

  • Keenan TM, Folch A (2008) Biomolecular gradients in cell culture systems. Lab Chip 8:34–57

    Article  Google Scholar 

  • Keenan TM, Hsu C-H, Folch A (2006) Microfluidic “jets” for generating steady-state gradients of soluble molecules on open surfaces. Appl Phys Lett 89:114103

    Article  Google Scholar 

  • Kim M, Yeon J, Park JK (2007) A microfluidic platform for 3-dimensional cell culture and cell-based assays. Biomed Microdevices 9(1):25–34

    Google Scholar 

  • Kim T, Holtz1 WJ, Park J, Keasling JD, Maharbiz MM (2009) Pattern formation in a synthetic microbial pathway driven by a microfluidic platform. In: Proceedings of 2009 international conference on microtechnologies in medicine and biology, Québec City, Canada, April 1–3, pp 110–111

  • Lin F, Saadi W, Rhee SW, Wang S-J, Mittal S, Jeon NL (2004) Generation of dynamic temporal and spatial concentration gradients using microfluidic devices. Lab Chip 4:164–167

    Article  Google Scholar 

  • Lou J, Shih CY, Lee E (2010) Diffusiophoresis of concentrated suspensions of spherical particles with charge-regulated surface: polarization effect with nonlinear Poisson-Boltzmann equation. Langmuir 26(1):47–55

    Google Scholar 

  • McLaughlin T, O’Leary DD (2005) Molecular gradients and development of retinotopic maps. Annu Rev Neurosci 28:327–355

    Article  Google Scholar 

  • Ranieri JP, Bellamkonda R, Jacob JG, Gardella JA, Aebischer P (1993) Selective neuronal cell attachment to a covalently patterned monoamine on fluorinated ethylene-propylene films. J Biomed Mater Res 27:917–925

    Article  Google Scholar 

  • Rosoff WJ, Urbach JS, Esrick MA, McAllister RG, Richards LJ, Goodhill GJ (2004) A new chemotaxis assay shows the extreme sensitivity of axons to molecular gradients. Nat Neurosci 7:678–682

    Article  Google Scholar 

  • Salmon ED, Saxton WM, Leslie RJ, Karow ML, Mclntosh JR (1984) Cytoplasm of embryonic cells of a sea urchin: video image analysis of fluorescence redistribution after photobleaching. Journal Cell Biol 99:2157–2164

    Article  Google Scholar 

  • Schoen I, Krammer H, Braun D (2009) Hybridization kinetics is different inside cells. Proc Natl Acad Sci USA 106(51):21649–21654

    Google Scholar 

  • Smith JT, Tomfohr JK, Wells MC, Beebe Jr., Kepler TB, Reichert WM (2004) Measurement of cell migration on surface-bound fibronectin gradients. Langmuir 20:8279–8286

  • Smith RL, Burgess RW, Collins SD (2009) Combinatorial cell microenvironment generator. In: Proceedings of 2009 international conference on microtechnologies in medicine and biology, Québec City, Canada, April 1–3

  • Walker GM, Sai J, Richmond A, Stremler M, Chung CY, Wikswo JP (2005) Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator. Lab chip 5:611–618

    Article  Google Scholar 

  • Weibel DB, Whitesides GM (2006) Applications of microfluidics in chemical biology. Current Opin Chem Biol 10:584–591

    Article  Google Scholar 

  • Winter JO, Schmidt CE (2002) Biomimetic strategies and applications in the nervous system. In: Dillow A, Lowman A (eds) Biomimetic materials and design: biointerfacial strategies, tissue engineering, and targeted drug delivery. Marcel-Dekker, New York, pp 375–415

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. D. Collins.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, R.L., Demers, C.J. & Collins, S.D. Microfluidic device for the combinatorial application and maintenance of dynamically imposed diffusional gradients. Microfluid Nanofluid 9, 613–622 (2010). https://doi.org/10.1007/s10404-010-0574-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-010-0574-7

Keywords

Navigation