Abstract
Control of particles/cells and the surrounding fluid is enabling toward the purification of complex cellular samples, which still remains a bottleneck for point-of-care diagnostic devices. We explore a newly developed approach to engineer fluid stream motion while simultaneously controlling particles using inertial lift force. We use inertial flow deformations induced by sequences of simple pillar microstructures to control the fluid stream. Instead of iterative experimental procedures to identify optimal sequences of structures, we use software that numerically predicts the total deformation function for any pillar sequence. Using this program, we engineer the cross-stream translation of a fluid stream to achieve solution exchange around particles, where both the particles and fluid stream remain focused and can be extracted at high purity. An extraction device, called a pillar separation device, is then designed and validated with suspensions of rigid particles to identify optimal operating parameters. At a flow rate of 250 µL/min, up to 96 % beads and 70.5 % of an initial buffer stream inputted into the system can be collected downstream in separate outlets, respectively, with 10.9 % buffer and 0.3 % bead contamination. This device was further applied to a functionalized bead bioassay, achieving high-yield and continuous separation of 98 % of biotin-coated beads from 72.2 % of extra FITC-biotin. In a last study, we performed the extraction of 80 % of leukocytes from lysed blood, which validates our platform can be applied on living cells and used for various functions of cellular sample preparation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akter F, Mie M, Kobatake E (2014) DNA-based immunoassays for sensitive detection of protein. Sens Actuators B: Chem 202:1248–1256
Amini H, Sollier E, Weaver WM, Di Carlo D (2012) Intrinsic particle-induced lateral transport in microchannels. PNAS 109(29):11593–11598
Amini H, Sollier E, Masaeli M, Xie Y, Ganapathysubramanian B, Stone HA, Di Carlo D (2013) Engineering fluid flow using sequenced microstructures. Nat Commun 4:1826
Amini H, Lee W, Di Carlo D (2014) Inertial microfluidics physics. Lab Chip 14:2739–2761
Augustsson P, Aberg LB, Sward-Nilsson A-MK, Laurell T (2009) Buffer medium exchange in continuous cell and particle streams using ultrasonic standing wave focusing. Microchim Acta 164:269–277
Chen J, Chen D, Yuan T, Xie Y, Chen X (2013) A microfluidic chip for direct and rapid trapping of white blood cells from whole blood. Biomicrofluidics 7:034106
Chin CD, Linder V, Sia SK (2012) Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip 12:2118–2134
Chung AJ, Pulido D, Oka JC, Masaeli M, Amini H, Di Carlo D (2013) Microstructure induced local helical vortices allow single-stream and long-term inertial focusing. Lab Chip 13:2942–2949
Cripps CM (1968) Rapid method for the estimation of plasma haemoglobin levels. J Clin Pathol 21(1):110–112
Davis JA, Inglis DW, Morton KJ, Lawrence DA, Huang LR, Chou SY, Sturm JC, Austin RH (2006) Deterministic hydrodynamics: taking blood apart. PNAS 103(40):14779–14784
Di Carlo D (2009) Inertial microfluidics. Lab Chip 9:3038–3046
Di Carlo D, Irimia D, Tompkins RG, Toner M (2007) Continuous inertial focusing, ordering and separation of particles in microchannels. PNAS 104:18892–18897
Di Carlo D, Edd JF, Irimia D, Tompkins RG, Toner M (2008) Equilibrium separation and filtration of particles using differential inertial focusing. Anal Chem 80:2204–2211
Di Carlo D, Edd JF, Humphry KJ, Stone H, Toner M (2009) Particle segregation and dynamics in confined flows. Phys Rev Lett 102:094503
Dudani JS, Gossett DR, Tan AP, Di Carlo D (2014) Mediating millisecond reaction time around particles and cells. Anal Chem. doi:10.1021/ac402920m
Gossett DR, Tse HTK, Dudani JS, Goda K, Woods TA, Graves SW, Di Carlo D (2012) Inertial manipulation and transfer of microparticles across laminar fluid streams. Small 8:2757–2764
Hur SC, Henderson-MacLennan NK, McCabe ERB, Di Carlo D (2011) Deformability-based cell classification and enrichment using inertial microfluidics. Lab Chip 11:912–920
Lee H, Park JE, Nam JM (2014) Bio-barcode gel assay for micro RNA. Nat Commun 5:3367
Mach AJ, Kim JH, Arshi A, Hur SC, Di Carlo D (2011) Automated cellular sample preparation using a centrifuge-on-a-chip. Lab Chip 11:2827–2834
Masaeli M, Sollier E, Amini H, Mao W, Camacho K, Doshi N, Mitragotri S, Alexeev A, Di Carlo D (2012) Continuous inertial focusing and separation of particles by shape. Phys Rev X 2:031017
Morijiri T, Sunahiro S, Senaha M, Yamada M, Seki M (2011) Sedimentation pinched flow fractionation for size and density based particle sorting in microchannels. Microfluid Nanofluid 11(1):105–110
Nunes JK, Wu C, Amini H, Owsley K, Di Carlo D, Stone HA (2014) Fabricating shaped microfibers with inertial microfluidics. Adv Mater 26(22):3712–3717
Pullaguria SR, Witek MA, Jackson JM, Lindell MAM, Hupert ML, Nesterova IV, Baird AE, Soper SA (2014) Parallel affinity-based isolation of leukocyte subsets using microfluidics: application for stroke diagnosis. Anal Chem 86(8):4058–4065
Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, Piech T, Patel PP, Chang L, Rivnak AJ, Ferrell EP, Randall JD, Provuncher GK, Walt DR, Duffy DC (2010) Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol 28:595–599
Shi W, Guo L, Kasdan H, Tai YC (2013) Four-part leukocyte differential count based on sheathless microflow cytometer and fluorescent dye assay. Lab Chip 13:1257–1265
Sollier E, Cubizolles M, Fouillet Y, Achard JL (2010) Fast and continuous plasma extraction from whole human blood based on expanding cell-free layer devices. Biomed Microdevices 12(3):485–497
Sollier E, Murray C, Maoddi P, Di Carlo D (2011) Rapid prototyping polymers for microfluidic devices and high pressure injections. Lab Chip 11:3752–3765
Sollier E, Go D, Che J, Gossett DR, O’Byrne S, Weaver WM, Kummer N, Rettig M, Goldman J, Nickols N, McCloskey S, Kulkarni R, Di Carlo D (2014) Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip 14:63–77
Spencer D, Elliott G, Morgan H (2014) A sheath-less combined optical and impedance micro-cytometer. Lab Chip 14:3064–3073
Stoeklein D, Wu CY, Owsley K, Xie Y, Di Carlo D, Ganapathysubramanian B (2014) Micropillar sequence designs for fundamental inertial flow transformations. Lab Chip. doi:10.1039/C4LC00653D
Watkins NN, Hassan U, Damhorst G, Ni H, Vaid A, Rodriguez W, Bashir R (2013) Microfluidic CD4 + and CD8 + T lymphocyte counters for point-of-care HIV diagnostics using whole blood. Sci Transl Med 5:214
Acknowledgments
This work is partially supported by NSF Grant #1307550. The authors would like to thank Dr. Oladunni Adeyiga for blood collection and all our volunteers for blood donation, Dr. Eric Tsang for his helpful advice with the Tecan Plate Reader, Dr. Ricky Chiu for his instructions on the Life Science UV/Vis spectrophotometer, Dr. M. Schibler and the California NanoSystems Institute Advanced Light Microscopy Core Facility for their assistance with the confocal studies.
Author information
Authors and Affiliations
Corresponding author
Additional information
Elodie Sollier and Hamed Amini have contributed equally to the study. Derek E. Go and Patrick A. Sandoz have contributed equally to the study.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Sollier, E., Amini, H., Go, D.E. et al. Inertial microfluidic programming of microparticle-laden flows for solution transfer around cells and particles. Microfluid Nanofluid 19, 53–65 (2015). https://doi.org/10.1007/s10404-015-1547-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10404-015-1547-7