Skip to main content
Log in

Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications

Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Although microfluidic micro-electromechanical systems (MEMS) are well suited to investigate the effects of mechanical force on large populations of cells, their high-throughput capabilities cannot be fully leveraged without optimizing the experimental conditions of the fluid and particles flowing through them. Parameters such as flow velocity and particle size are known to affect the trajectories of particles in microfluidic systems and have been studied extensively, but the effects of temperature and buffer viscosity are not as well understood. In this paper, we explored the effects of these parameters on the timing of our own cell-impact device, the μHammer, by first tracking the velocity of polystyrene beads through the device and then visualizing the impact of these beads. Through these assays, we find that the timing of our device is sensitive to changes in the ratio of inertial forces to viscous forces that particles experience while traveling through the device. This sensitivity provides a set of parameters that can serve as a robust framework for optimizing device performance under various experimental conditions, without requiring extensive geometric redesigns. Using these tools, we were able to achieve an effective throughput over 360 beads/s with our device, demonstrating the potential of this framework to improve the consistency of microfluidic systems that rely on precise particle trajectories and timing.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Data availability

Not applicable.

References

  • E.S. Asmolov, The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number. J. Fluid Mech. 381, 63–87 (1999)

    Article  Google Scholar 

  • A.A.S. Bhagat, S.S. Kuntaegowdanahalli, I. Papautsky, Inertial microfluidics for continuous particle filtration and extraction. Microfluid. Nanofluid. 7, 217–226 (2009)

    Article  Google Scholar 

  • A.A.S. Bhagat, H. Bow, H.W. Hou, S.J. Tan, J. Han, C.T. Lim, Microfluidics for cell separation. Med. Biol. Eng. Comput. 48, 999–1014 (2010a)

    Article  Google Scholar 

  • A.A.S. Bhagat, S.S. Kuntaegowdanahalli, N. Kaval, C.J. Seliskar, I. Papautsky, Inertial microfluidics for sheath-less high-throughput flow cytometry. Biomed. Microdevices 12, 187–195 (2010b)

    Article  Google Scholar 

  • M. Björnmalm, Y. Yan, F. Caruso, Engineering and evaluating drug delivery particles in microfluidic devices. J. Control. Release 190, 139–149 (2014)

    Article  Google Scholar 

  • A.J. Chung, D. Pulido, J.C. Oka, H. Amini, M. Masaeli, D. Di Carlo, Microstructure-induced helical vortices allow single-stream and long-term inertial focusing. Lab Chip 13, 2942–2949 (2013)

    Article  Google Scholar 

  • Y. Deng, S.P. Davis, F. Yang, K.S. Paulsen, M. Kumar, R. Sinnott DeVaux, X. Wang, D.S. Conklin, A. Oberai, J.I. Herschkowitz, Inertial microfluidic cell stretcher (iMCS): Fully automated, high-throughput, and near real-time cell mechanotyping. Small. 13, 1700705 (2017)

    Article  Google Scholar 

  • D. Desmaële, M. Boukallel, S. Régnier, Actuation means for the mechanical stimulation of living cells via microelectromechanical systems: A critical review. J. Biomech. 44, 1433–1446 (2011)

    Article  Google Scholar 

  • D. Di Carlo, Inertial microfluidics. Lab Chip 9, 3038–3046 (2009)

    Article  Google Scholar 

  • D. Di Carlo, D. Irimia, R.G. Tompkins, M. Toner, Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc. Nat. Acad. Sci. 104, 18892–18897 (2007)

    Article  Google Scholar 

  • J.S. Foster, K. Shields, M.R. Hoonejani, "Particle manipulation system with out-of-plane channel and variable cross section focusing element," U.S. Patent 9 962 702 B2, May 8, 2018

  • D.R. Gossett, T. Henry, S.A. Lee, Y. Ying, A.G. Lindgren, O.O. Yang, J. Rao, A.T. Clark, D. Di Carlo, Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc. Nat. Acad. Sci. 109, 7630–7635 (2012)

    Article  Google Scholar 

  • T. Han, L. Zhang, H. Xu, J. Xuan, Factory-on-chip: Modularised microfluidic reactors for continuous mass production of functional materials. Chem. Eng. J. 326, 765–773 (2017)

    Article  Google Scholar 

  • R. Hiorns, Polymer Handbook, 4th edn. (John Wiley and Sons, New York, 2000)

    Google Scholar 

  • K.J. Humphry, P.M. Kulkarni, D.A. Weitz, J.F. Morris, H.A. Stone, Axial and lateral particle ordering in finite Reynolds number channel flows. Phys. Fluids 22, 081703 (2010)

    Article  Google Scholar 

  • S.C. Hur, N.K. Henderson-MacLennan, E.R. McCabe, D. Di Carlo, Deformability-based cell classification and enrichment using inertial microfluidics. Lab Chip 11, 912–920 (2011)

    Article  Google Scholar 

  • S. Kahkeshani, H. Haddadi, D. Di Carlo, Preferred interparticle spacings in trains of particles in inertial microchannel flows. J. Fluid Mech. 786 (2016)

  • G.-B. Lee, C.-C. Chang, S.-B. Huang, R.-J. Yang, The hydrodynamic focusing effect inside rectangular microchannels. J. Micromechanics Microengineering. 16, 1024 (2006)

    Article  Google Scholar 

  • D. Lee, S.M. Nam, J.-a. Kim, D. Di Carlo, W. Lee, Active control of inertial focusing positions and particle separations enabled by velocity profile tuning with coflow systems. Anal. Chem. 90, 2902–2911 (2018)

    Article  Google Scholar 

  • A.M. Leshansky, A. Bransky, N. Korin, U. Dinnar, Tunable nonlinear viscoelastic “focusing” in a microfluidic device. Phys. Rev. Lett. 98, 234501 (2007)

    Article  Google Scholar 

  • O. Loh, A. Vaziri, H.D. Espinosa, The potential of MEMS for advancing experiments and modeling in cell mechanics. Exp. Mech. 49, 105–124 (2009)

    Article  Google Scholar 

  • Y. Luo, D. Chen, Y. Zhao, C. Wei, X. Zhao, W. Yue, R. Long, J. Wang, J. Chen, A constriction channel based microfluidic system enabling continuous characterization of cellular instantaneous Young's modulus. Sens. Actuators B: Chem. 202, 1183–1189 (2014)

    Article  Google Scholar 

  • M. Masaeli, E. Sollier, H. Amini, W. Mao, K. Camacho, N. Doshi, S. Mitragotri, A. Alexeev, D. Di Carlo, Continuous inertial focusing and separation of particles by shape. Phys. Rev. X. 2, 031017 (2012)

    Google Scholar 

  • K. Monkos, Viscosity of bovine serum albumin aqueous solutions as a function of temperature and concentration. Int. J. Biol. Macromol. 18, 61–68 (1996)

    Article  Google Scholar 

  • J.K. Nunes, C.Y. Wu, H. Amini, K. Owsley, D. Di Carlo, H.A. Stone, Fabricating shaped microfibers with inertial microfluidics. Adv. Mater. 26, 3712–3717 (2014)

    Article  Google Scholar 

  • J. Oakey, R.W. Applegate Jr., E. Arellano, D.D. Carlo, S.W. Graves, M. Toner, Particle focusing in staged inertial microfluidic devices for flow cytometry. Anal. Chem. 82, 3862–3867 (2010)

    Article  Google Scholar 

  • J. Oh, K. Kim, S.W. Won, C. Cha, A.K. Gaharwar, Š. Selimović, H. Bae, K.H. Lee, D.H. Lee, S.-H. Lee, Microfluidic fabrication of cell adhesive chitosan microtubes. Biomed. Microdevices 15, 465–472 (2013)

    Article  Google Scholar 

  • E. Ozkumur, A.M. Shah, J.C. Ciciliano, B.L. Emmink, D.T. Miyamoto, E. Brachtel, M. Yu, P.-i. Chen, B. Morgan, J. Trautwein, Inertial focusing for tumor antigen–dependent and–independent sorting of rare circulating tumor cells. Sci. Transl. Med 5, 179ra47 (2013)

    Article  Google Scholar 

  • L.H. Patterson, J.L. Walker, E. Rodriguez-Mesa, K. Shields, J.S. Foster, M.T. Valentine, A.M. Doyle, K.L. Foster, Investigating cellular response to impact with a microfluidic MEMS device. J. Microelectromech. Syst. (2019)

  • A.E. Reece, J. Oakey, Long-range forces affecting equilibrium inertial focusing behavior in straight high aspect ratio microfluidic channels. Phys. Fluids 28, 043303 (2016)

    Article  Google Scholar 

  • T. Sun, H. Morgan, Single-cell microfluidic impedance cytometry: A review. Microfluid. Nanofluid. 8, 423–443 (2010)

    Article  Google Scholar 

  • J.D. Tice, A.D. Lyon, R.F. Ismagilov, Effects of viscosity on droplet formation and mixing in microfluidic channels. Anal. Chim. Acta 507, 73–77 (2004)

    Article  Google Scholar 

  • S. Wang, X. Huang, C. Yang, Mixing enhancement for high viscous fluids in a microfluidic chamber. Lab Chip 11, 2081–2087 (2011)

    Article  Google Scholar 

  • X. Wang, M. Zandi, C.-C. Ho, N. Kaval, I. Papautsky, Single stream inertial focusing in a straight microchannel. Lab Chip 15, 1812–1821 (2015)

    Article  Google Scholar 

  • M.E. Warkiani, A.K.P. Tay, B.L. Khoo, X. Xiaofeng, J. Han, C.T. Lim, Malaria detection using inertial microfluidics. Lab Chip 15, 1101–1109 (2015)

    Article  Google Scholar 

  • F.M. White, I. Corfield, Viscous Fluid Flow (McGraw-Hill, New York, 2006)

    Google Scholar 

  • J. Zhang, S. Yan, D. Yuan, G. Alici, N.-T. Nguyen, M.E. Warkiani, W. Li, Fundamentals and applications of inertial microfluidics: A review. Lab Chip 16, 10–34 (2016)

    Article  Google Scholar 

Download references

Funding

This work was supported by the National Science Foundation with grants from the Division of Chemical, Bioengineering, Environmental, and Transport Systems (award number 1631656) and from the Division of Civil, Mechanical, and Manufacturing Innovation (award number 1254893).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luke H.C. Patterson.

Ethics declarations

Conflict of interest

The authors declare that they have no personal or institutional conflict of interest.

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patterson, L.H., Walker, J.L., Naivar, M.A. et al. Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications. Biomed Microdevices 22, 52 (2020). https://doi.org/10.1007/s10544-020-00508-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s10544-020-00508-1

Keywords

Navigation