Extended capabilities of pressure driven flow for microfluidics applications

Flow Stability

1. Cell perfusion and shear stress

Fluid shear stress is the tangential component of frictional forces generated at a surface (e.g., the vessel wall) by the flow of a viscous fluid (e.g., blood), and affects the physiology of the cells1. Conventional static cell culture does not allow reproducing such phenomenon while microfluidic is rising as an efficient tool for studying cell behavior under perfusion2.

Depending on the field of application, shear stress-related flow requirements can be different. Some studies exclude this parameter and other researchers are trying to reproduce in-vivo shear stress conditions. In both cases, precise and pulseless flow control is critical for repeatable results. While peristaltic pumps and syringe pumps generate pulsatile and unstable flows, pressure-driven pumps have shown the best performance.

2. Stable flow for monodisperse droplet generation

Droplet microfluidics has quickly become a central field of interest among the countless number of possibilities provided by microfluidics. As a femtoliter scale reactor3 with high-throughput processing capabilities (tens to thousands of hertz production), droplet microfluidics brings a promising future compared to µL scale 384 well plates. Biochemical analysis based on droplet microfluidics has been successfully reported (Droplet microfluidics in (bio)chemical analysis) and several companies have introduced dPCR systems in the market.

High scale emulsion production is well established in huge industries such as food, cosmetics, and particle synthesis but batch production has its limitations and in-line continuous droplet production provides many advantages:

  • Continuous production
  • Easy scalability with parallelization capability
  • Highly monodisperse droplet generation
  • Precise and flexible control of droplet size

In microfluidic devices, droplet size and generation rate are directly linked to the flow rates of the two phases4. The injection flow rate stability is thus critical for having repeatable reactor volume and reproducible results. Pressure pumps provide a more stable flow profile leading to better experimental data or production results.

Complex flow profile generation

The responsiveness of a pump is critical for many microfluidic applications.

Indeed, when an experiment needs to simulate biological or mathematical flow profiles, a highly responsive pump is necessary to generate sine waves, ramps, or aortic pressure-based flow profiles for instance.

Such flow profiles require ultra-fast responsiveness to be generated in a controlled way. Syringe pump technologies are not responsive enough to achieve such performance. A response time comparison between a high-precision syringe pump and the LineUP series of Fluigent (see figure) shows that it would be impossible to achieve a standard heartbeat pulsation simulation at 80bpm.

Check the OxyGEN software for automated protocol creation

1. Cost effective solution for sequential injection in cell perfusion application

Many microfluidic applications require switching between multiple solutions (such as samples or buffers) while maintaining a constant flow rate during the course of their experiment. The use of a single pressure pump (such as Fluigent’s LineUP, or MFCS series) associated with a sequential valve provide a high performance and compact solution in cell perfusion applications.

2. Flow rate and pressure monitoring

While Syringe pumps deduce the perfusion flow rate from a piston displacement, a pressure pump is generally associated with a flow sensor. When a microfluidic channel is clogged, a syringe pump continues to perfuse leading to an increase of pressure or leakages and in the worst case to the burst of the chip. The LineUP system is controlling and monitoring both pressure and flow rate with an easy way of limiting the pressure and/or flow rate. Many customers use our pumps for quality checks after chip production by monitoring pressure and flow rate while flowing the recently produced chip. Also, one could use these monitoring features as a control while an experiment is running.

Cell-Perfusion-System

For the complete application note, go to:
www.fluigent.com/application/cell-perfusion-delivery-with-pulse-free-flow/

References

  1. Chiu, J. and Chien, S. (2011). Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives. Physiological Reviews, 91(1), pp.327-387.
  2. Lu, H. et al. Microfluidic shear devices for quantitative analysis of cell adhesion. Anal. Chem.76, 5257–5264 (2004).
  3. Leman M, Abouakil F, Griffiths AD, Tabeling P. Droplet-based microfluidics at the femtolitre scale. Lab Chip. 2015 Feb 7;15(3):753-65. doi: 10.1039/c4lc01122h.
  4. SY Teh, R Lin, LH Hung, AP Lee. Droplet microfluidics. Lab on a Chip, 2008

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