Biomedical Microdevices

, Volume 12, Issue 6, pp 1027–1041 | Cite as

A low resistance microfluidic system for the creation of stable concentration gradients in a defined 3D microenvironment

  • Ovid C. Amadi
  • Matthew L. Steinhauser
  • Yuichi Nishi
  • Seok Chung
  • Roger D. Kamm
  • Andrew P. McMahon
  • Richard T. Lee
Article

Abstract

The advent of microfluidic technology allows control and interrogation of cell behavior by defining the local microenvironment with an assortment of biochemical and biophysical stimuli. Many approaches have been developed to create gradients of soluble factors, but the complexity of such systems or their inability to create defined and controllable chemical gradients has limited their widespread implementation. Here we describe a new microfluidic device which employs a parallel arrangement of wells and channels to create stable, linear concentration gradients in a gel region between a source and a sink well. Pressure gradients between the source and sink wells are dissipated through low resistance channels in parallel with the gel channel, thus minimizing the convection of solute in this region. We demonstrate the ability of the new device to quantitate chemotactic responses in a variety of cell types, yielding a complete profile of the migratory response and representing the total number of migrating cells and the distance each cell has migrated. Additionally we show the effect of concentration gradients of the morphogen Sonic hedgehog on the specification of differentiating neural progenitors in a 3-dimensional matrix.

Keywords

Microfluidic Concentration gradient Migration Chemotaxis Morphogen gradient Morphogenesis 

Supplementary material

10544_2010_9457_MOESM1_ESM.doc (58 kb)
ESM(DOC 58 kb)
10544_2010_9457_Fig6_ESM.jpg (319 kb)
Fig. S1

Fig. S1 Rearranged RC circuits used to calculate the time constants for pressure dissipation in the RC device. (a) This circuit represents the path from the source well to the sink well that passes through the reservoir channels and the source and sink reservoir. (b) This circuit represents the path from the source well to sink well that passes through the high resistance gel region (JPEG 318 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ovid C. Amadi
    • 1
    • 2
  • Matthew L. Steinhauser
    • 2
  • Yuichi Nishi
    • 3
  • Seok Chung
    • 4
  • Roger D. Kamm
    • 5
    • 6
  • Andrew P. McMahon
    • 3
    • 7
  • Richard T. Lee
    • 2
    • 7
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Cardiovascular DivisionBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of Molecular and Cellular BiologyHarvard UniversityCambridgeUSA
  4. 4.School of Mechanical EngineeringKorea UniversitySeoulSouth Korea
  5. 5.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  6. 6.Department of Mechanical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  7. 7.Harvard Stem Cell InstituteHarvard UniversityCambridgeUSA

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