Abstract
In this paper, a simple and robust design for a passive hydrodynamic cell sorter based on pinched flow-field fractionation is presented and analyzed. Two principal layouts of the sorter are discussed and investigated experimentally as well as numerically based on the dissipative particle dynamics (DPD) method. Experimentally, design 1 approximately sorts 87 % of the erythrocytes to their designated outlet, while 100 % of the leukocytes branch correctly. This also holds for design 2 differing merely in the direction of the outlet for erythrocytes, but here only 69 % of the red blood cells are redirected to the designated outlet. This behavior can be elucidated by employing DPD simulations, where erythrocytes advected with the flow are modeled explicitly. Our results suggest that if a cell sorter is designed to operate at high throughput, its layout may not entirely rely on commonly assumed idealizing conditions, because cells cannot be considered as point-like, isolated objects following definite stream lines. Hydrodynamic forces originating from the cells as extended objects must be taken into account.
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Abkarian M, Viallat A (2008) Vesicles and red blood cells in shear flow. Soft Matter 4:653–657
Boryczko K, Dzwinel W, Yuen DA (2003a) Dynamical clustering of red blood cells in capillary vessels. J Mol Mod 9(1):16–33
Boryczko K, Dzwinel W, Yuen DA (2003b) Clustering revealed in high-resolution simulations and visualization of multi-resolution features in fluid-particle models. Concurr Comput Pract Exp 15(2):101–116
Boryczko K, Dzwinel W, Yuen DA (2004) Modeling fibrin aggregation in blood flow with discrete-particles. Comput Method Prog Bio 75(3):181–194
Brenner T (2005) Polymer fabrication and microfluidic unit operations for medical diagnostics on a rotating disk. Thesis/dissertation. http://urn:nbn:de:bsz:25-opus-23062, http://www.freidok.uni-freiburg.de/volltexte/2306
Cherukat P, McLaughlin JB (1994) The inertial lift on a rigid sphere in a linear shear flow field near a flat wall. J Fluid Mech 263:1–18
Cherukat P, McLaughlin JB, Dandy DS (1999) A computational study of the inertial lift on a sphere in a linear shear flow field. Int J Multiphase Flow 25:15–33
Cox RG, Hsu SK (1977) The lateral migration of solid particles in a laminar flow near a plane. Int J Multiphase Flow 3:201–222
Cupelli C, Henrich B, Glatzel T, Moseler M, Zengerle R, Santer M (2008) Dynamic capillary wetting studied with dissipative particle dynamics. New J Phys 10(4):043009
Di Carlo D, Irimia D, Tompkins RG, Toner M (2007) Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc Natl Acad Sci USA 104(48):18892–18897
El-Kareh AW, Secomb TW (2000) A model for red blood cell motion in bifurcating microvessels. Int J Multiphase Flow 26:1545–1564
Español P, Warren PB (1995) Statistical-mechanics of dissipative particle dynamics. Europhys Lett 30(4):191–196
Fedosov DA, Caswell B, Karniadakis GE (2010a) Systematic coarse-graining of spectrin-level red blood cell models. Comput Method Appl Mech Eng 199:1937–1948
Fedosov DA, Caswell B, Karniadakis GE (2010b) A multiscale red blood cell model with accurate mechanics, rheology and dynamics. Biophys J 98:2215–2225
Groot RD, Warren PB (1997) Dissipative particle dynamics: bridging the gap between atomistic and mesoscopic simulation. J Chem Phys 107(11):4423–4435
Henrich B, Cupelli C, Moseler M, Zengerle R, Santer M (2007) An adhesive DPD wall model for dynamic wetting. Europhys Lett 80(6):60004
Howard M (2003) Shapiro practical flow cytometry, 4th edn. Wiley, New York (Published online 28 Jan 2005)
Liu Y, Liu WK (2006) Rheology of red blood cell aggregation by computer simulation. J Comput Phys 220(1):139–154
Lowe CP (1999) An alternative approach to dissipative particle dynamics. Europhys Lett 47(2):145–151
Marsh CA, Backx G, Ernst MH (1997) Static and dynamic properties of dissipative particle dynamics. Phys Rev E 56(2):1676–1691
Noguchi H, Gompper G (2005) Shape transitions of fluid vesicles and red blood cells in capillary flows. Proc Natl Acad Sci USA 102(40):14159–14164
Olla P (1999) Simplified model for red cell dynamics in small blood vessels. Phys Rev Lett 6(5):453–456
Peters EAJF (2004) Elimination of time step effects in DPD. Europhys Lett 66(3):311–317
Pozrikidis C (2003) Numerical simulation of the flow-induced deformation of red blood cells. Ann Biomed Eng 31:1194–1205
Riegger L et al (2006) Read-out concepts for multiplexed bead-based fluorescence immunoassays on centrifugal microfluidic platforms. Sens Actuators A 126:455–462
Roberts BW, Olbricht WL (2003) Flow-induced particulate separations. AIChE J 49(11):2842–2849
Roberts BW, Olbricht WL (2006) The distribution of freely suspended particles at microfluidic bifurcations. AIChE J 52(1):199–206
Rubinow SI, Keller JB (1999) The transverse force on a spinning sphere moving in a viscous fluid. J Fluid Mech 11:447–459
Saffman PG (1965) The lift on a small sphere in a slow shear flow. J Fluid Mech 22(2):385–400
Segré G, Silberberg A (1961) Radial particle displacements in Poisseuille flow of suspensions. Nature 189:209–210
Steiner T, Cupelli C, Zengerle R, Santer M (2009) Simulation of advanced microfluidic systems with dissipative particle dynamics. Microfluid Nanofluid 7:307–323
Sun C, Migliori C, Munn LL (2003) Red blood cells initiate leukocyte rolling in postcapillary expansions: a lattice boltzmann analysis. Biophys J 85:208–222
Takagi J, Yamada M, Yasuda M, Seki M (2005) Continuous particle separation in a microchannel having asymmetrically arranged multiple branches. Lab Chip 5(7):778–784
Takemura F, Magnaudet J (2003) The transverse force on clean and contaminated bubbles rising near a vertical wall at moderate Reynolds number. J Fluid Mech 495:235–253
Tokarev A, Panasenko G, Ataullakhanov F (2011) Segregation of flowing blood: mathematical description. Math Model Nat Phenom 6(5):281–319
Young B, Lowe JS, Stevens A, Heart JW (2006) Wheater’s functional histology, 5th edn. Churchill Livingstone, London
Worth Longest P, Kleinstreuer C, Buchanan JR (2004) Efficient computation of micro-particle dynamics including wall effects. Comput Fluids 33:577–601
Vattulainen I, Karttunen M, Besold G, Polson JM (2002) Integration schemes for dissipative particle dynamics simulations: from softly interacting systems towards hybrid models. J Chem Phys 116(10):3967–3979
Yamada M, Nakashima M, Seki M (2004) Pinched flow fractionation: continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. Anal Chem 76(18):5465–5471
Yamada M, Seki M (2005) Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. Lab Chip 5(11):1233–1239
Yamada M, Seki M (2006) Microfluidic particle sorter employing flow splitting and recombining. Anal Chem 78(4):1357–1362
Zeng L, Balachandar S, Fischer P (2005) Wall-induced forces on a rigid sphere at finite Reynolds number. J Fluid Mech 536:1–25
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The support of the Deutsche Forschungsgemeinschaft (DFG) for its support within the Priority Program SPP 1164 is gratefully acknowledged.
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Cupelli, C., Borchardt, T., Steiner, T. et al. Leukocyte enrichment based on a modified pinched flow fractionation approach. Microfluid Nanofluid 14, 551–563 (2013). https://doi.org/10.1007/s10404-012-1073-9
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DOI: https://doi.org/10.1007/s10404-012-1073-9