Inertial manipulation and transfer of microparticles across laminar fluid streams.

A general strategy for controlling particle movement across streams would enable new capabilities in single-cell analysis, solid-phase reaction control, and biophysics research. Transferring cells across streams is difficult to achieve in a well-controlled manner, since it requires precise control of fluid flow along with external force fields or precisely manufactured mechanical structures. Herein a strategy is introduced for particle transfer based on passive inertial lift forces and shifts in the distribution of these forces for channels with shifting aspect ratios. Uniquely, use of the dominant wall-effect lift parallel to the particle rotation direction is explored and utilized to achieve controllable cross-stream motion. In this way, particles are positioned to migrate across laminar streams and enter a new solution without significant disturbance of the interface at rates exceeding 1000 particles per second and sub-millisecond transfer times. The capabilities of rapid inertial solution exchange (RInSE) for preparation of hematological samples and other cellular assays are demonstrated. Lastly, improvements to inline flow cytometry after RInSE of excess fluorescent dye and focusing for downstream analysis are characterized. The described approach is simply applied to manipulating cells and particles and quickly exposing them to or removing them from a reacting solution, with broader applications in control and analysis of low affinity interactions on cells or particles.

[1]  A Lenshof,et al.  Emerging Clinical Applications of Microchip-Based Acoustophoresis , 2011, Journal of laboratory automation.

[2]  Yi Zhang,et al.  Continuous dielectrophoretic bacterial separation and concentration from physiological media of high conductivity. , 2011, Lab on a chip.

[3]  A. Bhagat,et al.  Enhanced particle filtration in straight microchannels using shear-modulated inertial migration , 2008 .

[4]  Thomas Laurell,et al.  Carrier medium exchange through ultrasonic particle switching in microfluidic channels. , 2005, Analytical chemistry.

[5]  D. Di Carlo,et al.  Continuous scalable blood filtration device using inertial microfluidics , 2010, Biotechnology and bioengineering.

[6]  Thomas Braschler,et al.  Dielectrophoresis-based particle exchanger for the manipulation and surface functionalization of particles. , 2008, Lab on a chip.

[7]  L. Sklar,et al.  Kinetic analysis of human flap endonuclease-1 by flow cytometry. , 1996, Biochemistry.

[8]  R. Tompkins,et al.  Continuous inertial focusing, ordering, and separation of particles in microchannels , 2007, Proceedings of the National Academy of Sciences.

[9]  Thomas Laurell,et al.  Buffer medium exchange in continuous cell and particle streams using ultrasonic standing wave focusing , 2009 .

[10]  Jeffrey D. Zahn,et al.  Microfluidic Devices for Continuous Blood Plasma Separation and Analysis During Pediatric Cardiopulmonary Bypass Procedures , 2006, ASAIO journal.

[11]  Jeffrey D Zahn,et al.  Continuous cytometric bead processing within a microfluidic device for bead based sensing platforms. , 2007, Lab on a chip.

[12]  Mehmet Toner,et al.  Particle focusing in staged inertial microfluidic devices for flow cytometry. , 2010, Analytical chemistry.

[13]  Jonas Persson,et al.  Acoustic microfluidic chip technology to facilitate automation of phage display selection , 2008, The FEBS journal.

[14]  H. Stone,et al.  Particle segregation and dynamics in confined flows. , 2009, Physical review letters.

[15]  Mehmet Toner,et al.  Controlled encapsulation of single-cells into monodisperse picolitre drops. , 2008, Lab on a chip.

[16]  Steven W Graves,et al.  Nozzle design parameters and their effects on rapid sample delivery in flow cytometry. , 2002, Cytometry.

[17]  Rakesh K Jain,et al.  A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood , 2007, Nature Protocols.

[18]  Nicole Pamme,et al.  Rapid on-chip multi-step (bio)chemical procedures in continuous flow--manoeuvring particles through co-laminar reagent streams. , 2008, Chemical communications.

[19]  Y. K. Cheung,et al.  1 Supplementary Information for : Microfluidics-based diagnostics of infectious diseases in the developing world , 2011 .

[20]  Helen H. Lee,et al.  Sample preparation: a challenge in the development of point-of-care nucleic acid-based assays for resource-limited settings. , 2007, The Analyst.

[21]  Minoru Seki,et al.  Millisecond treatment of cells using microfluidic devices via two-step carrier-medium exchange. , 2008, Lab on a chip.

[22]  Thomas Laurell,et al.  Decomplexing biofluids using microchip based acoustophoresis. , 2009, Lab on a chip.

[23]  D. Gossett,et al.  Particle focusing mechanisms in curving confined flows. , 2009, Analytical chemistry.

[24]  Nicole Pamme,et al.  Mobile magnetic particles as solid-supports for rapid surface-based bioanalysis in continuous flow. , 2009, Lab on a chip.

[25]  Evgeny S. Asmolov,et al.  The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number , 1999, Journal of Fluid Mechanics.

[26]  Steven W Graves,et al.  Flow cytometric analysis of ligand-receptor interactions and molecular assemblies. , 2002, Annual review of biophysics and biomolecular structure.

[27]  Samuel K Sia,et al.  Lab-on-a-chip devices for global health: past studies and future opportunities. , 2007, Lab on a chip.

[28]  Louis Scampavia,et al.  Coaxial flow mixer for real‐time monitoring of cellular responses in flow cytometry , 1996 .

[29]  D. Di Carlo,et al.  Sheathless inertial cell ordering for extreme throughput flow cytometry. , 2010, Lab on a chip.

[30]  H. Shapiro Practical Flow Cytometry: Shapiro/Flow Cytometry 4e , 2005 .

[31]  Robert W Barber,et al.  Continuous cell washing and mixing driven by an ultrasound standing wave within a microfluidic channel. , 2004, Lab on a chip.

[32]  R. Tompkins,et al.  Equilibrium separation and filtration of particles using differential inertial focusing. , 2008, Analytical chemistry.

[33]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[34]  Martin Dufva,et al.  Capture of DNA in microfluidic channel using magnetic beads: Increasing capture efficiency with integrated microfluidic mixer , 2007 .

[35]  C. Kappe,et al.  Rapid solid-phase synthesis of a calmodulin-binding peptide using controlled microwave irradiation , 2007, Nature Protocols.

[36]  R. Fair,et al.  An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. , 2004, Lab on a chip.

[37]  Dino Di Carlo,et al.  Dynamic self-assembly and control of microfluidic particle crystals , 2010, Proceedings of the National Academy of Sciences.

[38]  David W Inglis,et al.  Crossing microfluidic streamlines to lyse, label and wash cells. , 2008, Lab on a chip.

[39]  L. G. Leal,et al.  Inertial migration of rigid spheres in two-dimensional unidirectional flows , 1974, Journal of Fluid Mechanics.

[40]  Nicole K Henderson-Maclennan,et al.  Deformability-based cell classification and enrichment using inertial microfluidics. , 2011, Lab on a chip.

[41]  Søren L Pedersen,et al.  Microwave heating in solid-phase peptide synthesis. , 2012, Chemical Society reviews.