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Microfluidics and Nanofluidics

, Volume 15, Issue 1, pp 65–71 | Cite as

Maintaining stimulant waveforms in large-volume microfluidic cell chambers

  • Xinyu Zhang
  • Raghuram Dhumpa
  • Michael G. Roper
Research Paper

Abstract

Stimulation of cells with temporal waveforms can be used to observe the frequency-dependent nature of cellular responses. The ability to produce and maintain the temporal waveforms in spite of the broadening processes that occur as the wave travels through the microfluidic system is critical for observing dynamic behaviors. Broadening of waves in microfluidic channels has been examined, but the effect that large-volume cell chambers have on the waves has not. In this report, a sinusoidal glucose wave delivered to a 1-mm diameter cell chamber using various microfluidic channel structures was simulated by finite element analysis with the goal of minimizing the broadening of the waveform in the chamber and maximizing the homogeneity of the concentration in the chamber at any given time. Simulation results indicated that increasing the flow rate was the most effective means to achieve these goals, but at a given volumetric flow rate, geometries that deliver the waveform to multiple regions in the chamber while maintaining a high linear velocity produced sufficient results. A 4-inlet geometry with a 220-μm channel width gave the best result in the simulation and was used to deliver glucose waveforms to a population of pancreatic islets of Langerhans. The result was a stronger and more robust synchronization of the islet population as compared with when a non-optimized chamber was used. This general strategy will be useful in other microfluidic systems examining the frequency-dependence nature of cellular behavior.

Keywords

Dynamic stimulation Microfluidic perfusion Finite element analysis Broadening and delay Islets of Langerhans 

Notes

Acknowledgments

This work was supported in part by a grant from the National Institutes of Health (R01 DK080714). The authors thank Tuan Truong for help with isolating islets of Langerhans.

References

  1. Azizi F, Mastrangelo CH (2008) Generation of dynamic chemical signals with pulse code modulators. Lab Chip 8:907–912CrossRefGoogle Scholar
  2. Chou HF, Ipp E (1990) Pulsatile insulin secretion in isolated rat islets. Diabetes 39:112–117CrossRefGoogle Scholar
  3. Clark AM, Sousa KM, Chisolm CN, MacDougald OA, Kennedy RT (2010) Reversibly sealed multilayer microfluidic device for integrated cell perfusion and on-line chemical analysis of cultured adipocyte secretions. Anal Bio Chem 397:2939–2947CrossRefGoogle Scholar
  4. Danino T, Mondragon-Palomino O, Tsimring L, Hasty J (2010) A synchronized quorum of genetic clocks. Nature 463:326–330CrossRefGoogle Scholar
  5. Dhumpa R, Roper MG (2012) Temporal gradients in microfluidic systems to probe cellular dynamics: a review. Anal Chim Acta 743:9–18CrossRefGoogle Scholar
  6. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3440–3450Google Scholar
  7. Jovic A, Howell B, Cote M, Wade SM, Mehta K, Miyawaki A, Neubig RR, Linderman JJ, Takayama S (2010) Phase-locked signals elucidate circuit architecture of an oscillatory pathway. PLoS Comput Biol 6:e1001040MathSciNetCrossRefGoogle Scholar
  8. King KR, Wang S, Jayaraman A, Yarmush ML, Toner M (2008) Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments. Lab Chip 8:107–116CrossRefGoogle Scholar
  9. Lucchetta EM, Lee JH, Fu LA, Patel NH, Ismagilov RF (2005) Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature 434:1134–1138CrossRefGoogle Scholar
  10. Mohammed JS, Wang Y, Harvat TA, Oberholzer J, Eddington DT (2009) Microfluidic device for multimodal characterization of pancreatic islets. Lab Chip 9:97–106CrossRefGoogle Scholar
  11. Mondragon-Palomino O, Danino T, Selimkhanov J, Tsimring L, Hasty J (2011) Entrainment of a population of synthetic genetic oscillators. Science 333:1315–1319MathSciNetCrossRefGoogle Scholar
  12. Sankar KS, Green BJ, Crocker AR, Verity JE, Altamentova SM et al (2011) Culturing pancreatic islets in microfluidic flow enhances morphology of the associated endothelial cells. PLoS ONE 6:e24904CrossRefGoogle Scholar
  13. Sturis J, Pugh WL, Tang JP, Ostrega DM, Polonsky JS, Polonsky KS (1994) Alterations in pulsatile insulin secretion in the Zucker diabetic fatty rat. Am J Physiol 267:E250–E259Google Scholar
  14. Xie Y, Wang Y, Chen L, Mastrangelo CH (2008) Fourier microfluidics. Lab Chip 8:779–785CrossRefGoogle Scholar
  15. Zhang XY, Grimley A, Bertram R, Roper MG (2010) Microfluidic system for generation of sinusoidal glucose waveforms for entrainment of islets of Langerhans. Anal Chem 82:6704–6711CrossRefGoogle Scholar
  16. Zhang XY, Daou A, Truong T, Bertram R, Roper MG (2011) Synchronization of mouse islets of Langerhans by glucose waveforms. Am J Physiol Endocrinol Metab 301:E742–E747CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Xinyu Zhang
    • 1
  • Raghuram Dhumpa
    • 1
  • Michael G. Roper
    • 1
  1. 1.Department of Chemistry and BiochemistryFlorida State UniversityTallahasseeUSA

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