Lateral Displacement

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German Drazer - One of the best experts on this subject based on the ideXlab platform.

  • liquid based stationary phase for deterministic Lateral Displacement separation in microfluidics
    Soft Matter, 2017
    Co-Authors: Shahab Shojaeizadeh, German Drazer
    Abstract:

    Deterministic Lateral Displacement (DLD) is a promising separation scheme in microfluidic systems. In traditional DLD, a periodic array of solid posts induces the separative migration of suspended particles moving through the system. Here, we present a radical departure from traditional DLD systems and use an array of anchored liquid-bridges as the stationary phase in the DLD device. The liquid-bridges are created between two parallel plates and anchored to the bottom one by cylindrical wells. We show that the non-linear particle dynamics observed in traditional DLD systems is also present in the anchored-liquid case, enabling analogous size-based separation of suspended particles. The use of liquid-bridges as the stationary phase presents additional possibilities in separation technologies, potentially eliminating or significantly reducing clogging, enabling renewable and/or reconfigurable systems, allowing a different set of fabrication methods and providing alternative ways to separate particles based on their interaction with liquid-liquid interfaces. Some of these advantages could also extend to filtration methods based on similar liquid-based stationary phases.

  • centrifuge based deterministic Lateral Displacement separation
    Microfluidics and Nanofluidics, 2016
    Co-Authors: Mingliang Jiang, Aaron D Mazzeo, German Drazer
    Abstract:

    This work investigates the migration of spherical particles of different sizes in a centrifuge-driven deterministic Lateral Displacement device. Specifically, we use a scaled-up model to study the motion of suspended particles through a square array of cylindrical posts under the action of centrifugation. Experiments show that separation of particles by size is possible depending on the orientation of the driving acceleration with respect to the array of posts (forcing angle). We focus on the fractionation of binary suspensions and measure the separation resolution at the outlet of the device for different forcing angles. We found excellent resolution at intermediate forcing angles, when large particles are locked to move at small migration angles, but smaller particles follow the forcing angle more closely. Finally, we show that reducing the initial concentration (number) of particles, approaching the dilute limit of single particles, leads to increased resolution in the separation.

  • centrifugal deterministic Lateral Displacement separation system
    arXiv: Soft Condensed Matter, 2015
    Co-Authors: Mingliang Jiang, Aaron D Mazzeo, German Drazer
    Abstract:

    This work investigates the migration of spherical particles of different sizes in a centrifuge-driven deterministic Lateral Displacement (c-DLD) device. Specifically, we use a scaled-up model to study the motion of suspended particles through a square array of cylindrical posts under the action of centrifugation. Experiments show that separation of particles by size is possible depending on the orientation of the driving acceleration with respect to the array of posts (forcing angle). We focus on the fractionation of binary suspensions and measure the separation resolution at the outlet of the device for different forcing angles. We found excellent resolution at intermediate forcing angles, when large particles are locked to move at small migration angles but smaller particles follow the forcing angle more closely. Finally, we show that reducing the initial concentration (number) of particles, approaching the dilute limit of single particles, leads to increased resolution in the separation.

  • electrokinetically driven deterministic Lateral Displacement for particle separation in microfluidic devices
    Microfluidics and Nanofluidics, 2015
    Co-Authors: Srinivas Hanasoge, Raghavendra Devendra, F J Diez, German Drazer
    Abstract:

    An electrokinetically driven deterministic Lateral Displacement device is proposed for the continuous, two-dimensional fractionation of suspensions in microfluidic platforms. The suspended species are driven through an array of regularly spaced cylindrical posts by applying an electric field across the device. We explore the entire range of orientations of the driving field with respect to the array of obstacles and show that, at specific forcing angles, particles of different size migrate in different directions, thus enabling continuous, two-dimensional separation. We discuss a number of features observed in the motion of the particles, including directional locking and sharp transitions between migration angles upon variations in the direction of the force, that are advantageous for high-resolution two-dimensional separation. A simple model based on individual particle–obstacle interactions accurately describes the migration angle of the particles depending on the orientation of the driving field and can be used to reconfigure the electric field depending on the composition of the samples.

  • fractionation by shape in deterministic Lateral Displacement microfluidic devices
    Microfluidics and Nanofluidics, 2015
    Co-Authors: Kostyantyn Budzan, Mingliang Jiang, German Drazer
    Abstract:

    We investigate the migration of particles of different geometrical shapes and sizes in a scaled-up model of a gravity-driven deterministic Lateral Displacement (g-DLD) device. Specifically, particles move through a square array of cylindrical posts as they settle in a quiescent fluid under the action of gravity. We performed experiments that cover a broad range of orientations of the driving force (gravity) with respect to the columns (or rows) in the square array of posts. We observe that as the forcing angle increases, particles initially locked to move parallel to the columns in the array begin to move across the columns of obstacles and migrate at angles different from zero. We measure the probability that a particle would move across a column of obstacles, and define the critical angle θ c as the forcing angle at which this probability is 1/2. We show that critical angle depends on both particle size and shape, thus enabling both size- and shape-based separations. Finally, we show that using the diameter of the inscribed sphere as the characteristic size of the particles, the corresponding critical angle becomes independent of particle shape and the relationship between them is linear. This linear and possibly universal behavior of the critical angle as a function of the diameter of the inscribed sphere of the particles could provide guidance in the design and optimization of g-DLD devices used for shape-based separation.

Jonas O Tegenfeldt - One of the best experts on this subject based on the ideXlab platform.

  • open channel deterministic Lateral Displacement for particle and cell sorting
    Lab on a Chip, 2017
    Co-Authors: Trung S H Tran, Jason P Beech, Jonas O Tegenfeldt
    Abstract:

    We present the use of capillary driven flow over patterned surfaces to achieve cheap and simple, but powerful separation of biologically relevant particle systems. The wide use of microfluidics is often hampered by the propensity for devices to clog due to the small channel sizes and the inability to access the interior of devices for cleaning. Often the devices can only be used for a limited duration and most frequently only once. In addition the cost and power requirements of flow control equipment limits the wider spread of the devices. We address these issues by presenting a simple particle- and cell-sorting scheme based on controlled fluid flow on a patterned surface. The open architecture makes it highly robust and easy to use. If clogging occurs it is straightforward to rinse the device and reuse it. Instead of external mechanical pumps, paper is used as a capillary pump. The different fractions are deposited in the paper and can subsequently be handled independently by simply cutting the paper for downstream processing and analyses. The sorting, based on deterministic Lateral Displacement, performs equivalently well in comparison with standard covered devices. We demonstrate successful separation of cancer cells and parasites from blood with good viability and with relevance for diagnostics and sample preparation. Sorting a mixture of soil and blood, we show the potential for forensic applications.

  • separation of parasites from human blood using deterministic Lateral Displacement
    Lab on a Chip, 2011
    Co-Authors: Stefan H Holm, Jason P Beech, Jonas O Tegenfeldt, Michael P Barrett
    Abstract:

    We present the use of a simple microfluidic technique to separate living parasites from human blood. Parasitic trypanosomatids cause a range of human and animal diseases. African trypanosomes, responsible for human African trypanosomiasis (sleeping sickness), live free in the blood and other tissue fluids. Diagnosis relies on detection and due to their often low numbers against an overwhelming background of predominantly red blood cells it is crucial to separate the parasites from the blood. By modifying the method of deterministic Lateral Displacement, confining parasites and red blood cells in channels of optimized depth which accentuates morphological differences, we were able to achieve separation thus offering a potential route to diagnostics.

  • tipping the balance of deterministic Lateral Displacement devices using dielectrophoresis
    Lab on a Chip, 2009
    Co-Authors: Jason P Beech, Peter Jonsson, Jonas O Tegenfeldt
    Abstract:

    We report the use of dielectrophoresis (DEP) to achieve tunability, improve dynamic range and open up for the separation of particles with regard to parameters other than hydrodynamic size in deterministic Lateral Displacement (DLD) devices. DLD devices have been shown capable of rapidly and continuously separating micrometer sized plastic spheres by size with a resolution of 20 nm in diameter and of being able to handle the separation of biological samples as wide ranging as bacterial artificial chromosomes and blood cells. DEP, while not exhibiting the same resolution in size separation as DLD, has the benefit of being easy to tune and can, by choosing the frequency, be used to probe a variety of particle properties. By combining DLD and DEP we open up for the advantages, while avoiding the drawbacks, of the two techniques. We present a proof of principle in which the critical size for separation of polystyrene beads is tuned in the range 2-6 microm in a single device by the application of moderate (100 V cm(-1)), low frequency (100 Hz) AC electric fields. The behaviour of the device was further investigated by performing simulations of particle trajectories, the results of which were in good qualitative agreement with experiments, indicating the potential of the method for tunable, high-resolution separations with respect to both size and polarisability.

  • multidirectional sorting modes in deterministic Lateral Displacement devices
    Physical Review E, 2008
    Co-Authors: Brian R Long, Jason P Beech, Martin Heller, Heiner Linke, Henrik Bruus, Jonas O Tegenfeldt
    Abstract:

    Deterministic Lateral Displacement (DLD) devices separate micrometer-scale particles in solution based on their size using a laminar microfluidic flow in an array of obstacles. We investigate array geometries with rational row-shift fractions in DLD devices by use of a simple model including both advection and diffusion. Our model predicts multidirectional sorting modes that could be experimentally tested in high-throughput DLD devices containing obstacles that are much smaller than the separation between obstacles.

Gustavo Stolovitzky - One of the best experts on this subject based on the ideXlab platform.

  • deterministic Lateral Displacement challenges and perspectives
    ACS Nano, 2020
    Co-Authors: Axel Hochstetter, Rohan Vernekar, Robert H Austin, Holger Becker, Jason P Beech, Dmitry A Fedosov, Gerhard Gompper, Sungcheol Kim, Joshua T Smith, Gustavo Stolovitzky
    Abstract:

    The advent of microfluidics in the 1990s promised a revolution in multiple industries from healthcare to chemical processing. Deterministic Lateral Displacement (DLD) is a continuous-flow microflui...

  • broken flow symmetry explains the dynamics of small particles in deterministic Lateral Displacement arrays
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Sungcheol Kim, Robert H Austin, Joshua T Smith, Benjamin H Wunsch, Gustavo Stolovitzky
    Abstract:

    Deterministic Lateral Displacement (DLD) is a technique for size fractionation of particles in continuous flow that has shown great potential for biological applications. Several theoretical models have been proposed, but experimental evidence has demonstrated that a rich class of intermediate migration behavior exists, which is not predicted. We present a unified theoretical framework to infer the path of particles in the whole array on the basis of trajectories in a unit cell. This framework explains many of the unexpected particle trajectories reported and can be used to design arrays for even nanoscale particle fractionation. We performed experiments that verify these predictions and used our model to develop a condenser array that achieves full particle separation with a single fluidic input.

  • nanoscale Lateral Displacement arrays for the separation of exosomes and colloids down to 20 nm
    Nature Nanotechnology, 2016
    Co-Authors: Benjamin H Wunsch, Robert H Austin, Joshua T Smith, Gustavo Stolovitzky, Stacey M Gifford, Chao Wang, Markus Brink, Robert L Bruce
    Abstract:

    Lateral Displacement pillar arrays can now be used to separate nanoscale colloids including exosomes, offering new opportunities for on-chip sorting and quantification of biocolloids by size.

  • nanoscale Lateral Displacement arrays for the separation of exosomes and colloids down to 20 nm
    Nature Nanotechnology, 2016
    Co-Authors: Benjamin H Wunsch, Robert H Austin, Joshua T Smith, Gustavo Stolovitzky, Stacey M Gifford, Chao Wang, Markus Brink, Robert L Bruce
    Abstract:

    Lateral Displacement pillar arrays can now be used to separate nanoscale colloids including exosomes, offering new opportunities for on-chip sorting and quantification of biocolloids by size. Deterministic Lateral Displacement (DLD) pillar arrays are an efficient technology to sort, separate and enrich micrometre-scale particles, which include parasites1, bacteria2, blood cells3 and circulating tumour cells in blood4. However, this technology has not been translated to the true nanoscale, where it could function on biocolloids, such as exosomes. Exosomes, a key target of ‘liquid biopsies’, are secreted by cells and contain nucleic acid and protein information about their originating tissue5. One challenge in the study of exosome biology is to sort exosomes by size and surface markers6,7. We use manufacturable silicon processes to produce nanoscale DLD (nano-DLD) arrays of uniform gap sizes ranging from 25 to 235 nm. We show that at low Peclet (Pe) numbers, at which diffusion and deterministic Displacement compete, nano-DLD arrays separate particles between 20 to 110 nm based on size with sharp resolution. Further, we demonstrate the size-based Displacement of exosomes, and so open up the potential for on-chip sorting and quantification of these important biocolloids.

David W. Inglis - One of the best experts on this subject based on the ideXlab platform.

  • deterministic Lateral Displacement the next generation car t cell processing
    SLAS TECHNOLOGY: Translating Life Sciences Innovation, 2018
    Co-Authors: Roberto Camposgonzalez, David W. Inglis, J C Sturm, Curt I Civin, Alison Skelley, Khushroo Gandhi, Tony Ward
    Abstract:

    Reliable cell recovery and expansion are fundamental to the successful scale-up of chimeric antigen receptor (CAR) T cells or any therapeutic cell-manufacturing process. Here, we extend our previous work in whole blood by manufacturing a highly parallel deterministic Lateral Displacement (DLD) device incorporating diamond microposts and moving into processing, for the first time, apheresis blood products. This study demonstrates key metrics of cell recovery (80%) and platelet depletion (87%), and it shows that DLD T-cell preparations have high conversion to the T-central memory phenotype and expand well in culture, resulting in twofold greater central memory cells compared to Ficoll-Hypaque (Ficoll) and direct magnetic approaches. In addition, all samples processed by DLD converted to a majority T-central memory phenotype and did so with less variation, in stark contrast to Ficoll and direct magnetic prepared samples, which had partial conversion among all donors (<50%). This initial comparison of T-cell function infers that cells prepared via DLD may have a desirable bias, generating significant potential benefits for downstream cell processing. DLD processing provides a path to develop a simple closed system that can be automated while simultaneously addressing multiple steps when there is potential for human error, microbial contamination, and other current technical challenges associated with the manufacture of therapeutic cells.

  • Anisotropic permeability in deterministic Lateral Displacement arrays
    Lab on a chip, 2017
    Co-Authors: Rohan Vernekar, Timm Kruger, Kevin Loutherback, Keith Morton, David W. Inglis
    Abstract:

    We uncover anisotropic permeability in microfluidic deterministic Lateral Displacement (DLD) arrays. A DLD array can achieve high-resolution bimodal size-based separation of microparticles, including bioparticles, such as cells. For an application with a given separation size, correct device operation requires that the flow remains at a fixed angle to the obstacle array. We demonstrate via experiments and lattice-Boltzmann simulations that subtle array design features cause anisotropic permeability. Anisotropic permeability indicates the microfluidic array's intrinsic tendency to induce an undesired Lateral pressure gradient. This can cause an inclined flow and therefore local changes in the critical separation size. Thus, particle trajectories can become unpredictable and the device useless for the desired separation task. Anisotropy becomes severe for arrays with unequal axial and Lateral gaps between obstacle posts and highly asymmetric post shapes. Furthermore, of the two equivalent array layouts employed with the DLD, the rotated-square layout does not display intrinsic anisotropy. We therefore recommend this layout over the easier-to-implement parallelogram layout. We provide additional guidelines for avoiding adverse effects of anisotropy on the DLD.

  • anisotropic permeability in deterministic Lateral Displacement arrays
    arXiv: Fluid Dynamics, 2016
    Co-Authors: Rohan Vernekar, Timm Kruger, Kevin Loutherback, Keith Morton, David W. Inglis
    Abstract:

    We investigate anisotropic permeability of microfluidic deterministic Lateral Displacement (DLD) arrays. A DLD array can achieve high-resolution bimodal size-based separation of micro-particles, including bioparticles such as cells. Correct operation requires that the fluid flow remains at a fixed angle with respect to the periodic obstacle array. We show via experiments and lattice-Boltzmann simulations that subtle array design features cause anisotropic permeability. The anisotropy, which indicates the array's intrinsic tendency to induce an undesired Lateral pressure gradient, can lead to off-axis flows and therefore local changes in the critical separation size. Thus, particle trajectories can become unpredictable and the device useless for the desired separation duty. We show that for circular posts the rotated-square layout, unlike the parallelogram layout, does not suffer from anisotropy and is the preferred geometry. Furthermore, anisotropy becomes severe for arrays with unequal axial and Lateral gaps between obstacle posts and highly asymmetrical post shapes.

  • scaling deterministic Lateral Displacement arrays for high throughput and dilution free enrichment of leukocytes
    Journal of Micromechanics and Microengineering, 2011
    Co-Authors: David W. Inglis, Megan S Lord, Robert E Nordon
    Abstract:

    A disposable device for fractionation of blood into its components that is simple to operate and provides throughput of greater than 1 mL min−1 is highly sought after in medical diagnostics and therapies. This paper describes a device with parallel deterministic Lateral Displacement devices for enrichment of leukocytes from blood. We show capture of 98% and approximately ten-fold enrichment of leukocytes in whole blood. We demonstrate scaling up through the integration of six parallel devices to achieve a flow rate of 115 µL of undiluted blood per minute per atmosphere of applied pressure.

  • highly accurate deterministic Lateral Displacement device and its application to purification of fungal spores
    Biomicrofluidics, 2010
    Co-Authors: David W. Inglis, Nick Herman, Graham Vesey
    Abstract:

    We have designed, built, and evaluated a microfluidic device that uses deterministic Lateral Displacement for size-based separation. The device achieves almost 100% purity and recovery in continuously sorting two, four, and six micrometer microspheres. We have applied this highly efficient device to the purification of fungal (Aspergillus) spores that are spherical (∼4 μm diameter) with a narrow size distribution. Such separation directly from culture using unfiltered A. niger suspensions is difficult due to a high level of debris. The device produces a two to three increase in the ratio of spores to debris as measured by light scatter in a flow cytometer. The procedure is feasible at densities up to 4.4×106 spores/ml. This is one of the first studies to apply microfluidic techniques to spore separations and has demonstrated that a passive separation system could significantly reduce the amount of debris in a suspension of fungal spores with virtually no loss of spore material.

Robert H Austin - One of the best experts on this subject based on the ideXlab platform.

  • deterministic Lateral Displacement challenges and perspectives
    ACS Nano, 2020
    Co-Authors: Axel Hochstetter, Rohan Vernekar, Robert H Austin, Holger Becker, Jason P Beech, Dmitry A Fedosov, Gerhard Gompper, Sungcheol Kim, Joshua T Smith, Gustavo Stolovitzky
    Abstract:

    The advent of microfluidics in the 1990s promised a revolution in multiple industries from healthcare to chemical processing. Deterministic Lateral Displacement (DLD) is a continuous-flow microflui...

  • broken flow symmetry explains the dynamics of small particles in deterministic Lateral Displacement arrays
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Sungcheol Kim, Robert H Austin, Joshua T Smith, Benjamin H Wunsch, Gustavo Stolovitzky
    Abstract:

    Deterministic Lateral Displacement (DLD) is a technique for size fractionation of particles in continuous flow that has shown great potential for biological applications. Several theoretical models have been proposed, but experimental evidence has demonstrated that a rich class of intermediate migration behavior exists, which is not predicted. We present a unified theoretical framework to infer the path of particles in the whole array on the basis of trajectories in a unit cell. This framework explains many of the unexpected particle trajectories reported and can be used to design arrays for even nanoscale particle fractionation. We performed experiments that verify these predictions and used our model to develop a condenser array that achieves full particle separation with a single fluidic input.

  • nanoscale Lateral Displacement arrays for the separation of exosomes and colloids down to 20 nm
    Nature Nanotechnology, 2016
    Co-Authors: Benjamin H Wunsch, Robert H Austin, Joshua T Smith, Gustavo Stolovitzky, Stacey M Gifford, Chao Wang, Markus Brink, Robert L Bruce
    Abstract:

    Lateral Displacement pillar arrays can now be used to separate nanoscale colloids including exosomes, offering new opportunities for on-chip sorting and quantification of biocolloids by size.

  • nanoscale Lateral Displacement arrays for the separation of exosomes and colloids down to 20 nm
    Nature Nanotechnology, 2016
    Co-Authors: Benjamin H Wunsch, Robert H Austin, Joshua T Smith, Gustavo Stolovitzky, Stacey M Gifford, Chao Wang, Markus Brink, Robert L Bruce
    Abstract:

    Lateral Displacement pillar arrays can now be used to separate nanoscale colloids including exosomes, offering new opportunities for on-chip sorting and quantification of biocolloids by size. Deterministic Lateral Displacement (DLD) pillar arrays are an efficient technology to sort, separate and enrich micrometre-scale particles, which include parasites1, bacteria2, blood cells3 and circulating tumour cells in blood4. However, this technology has not been translated to the true nanoscale, where it could function on biocolloids, such as exosomes. Exosomes, a key target of ‘liquid biopsies’, are secreted by cells and contain nucleic acid and protein information about their originating tissue5. One challenge in the study of exosome biology is to sort exosomes by size and surface markers6,7. We use manufacturable silicon processes to produce nanoscale DLD (nano-DLD) arrays of uniform gap sizes ranging from 25 to 235 nm. We show that at low Peclet (Pe) numbers, at which diffusion and deterministic Displacement compete, nano-DLD arrays separate particles between 20 to 110 nm based on size with sharp resolution. Further, we demonstrate the size-based Displacement of exosomes, and so open up the potential for on-chip sorting and quantification of these important biocolloids.

  • Improved performance of deterministic Lateral Displacement arrays with triangular posts
    Microfluidics and Nanofluidics, 2010
    Co-Authors: Kevin Loutherback, Robert H Austin, Kevin S. Chou, Jonathan Newman, Jason Puchalla, James C. Sturm
    Abstract:

    Deterministic Lateral Displacement arrays have shown great promise for size-based particle analysis and purification in medicine and biology. Here, we demonstrate that the use of an array of triangular rather than circular posts significantly enhances the performance of these devices by reducing clogging, lowering hydrostatic pressure requirements, and increasing the range of Displacement characteristics. Experimental data and theoretical models are presented to create a compelling argument that future designs of deterministic Lateral Displacement arrays should employ triangular posts. The effect of practical considerations, such as vertex rounding, post size, and shape, is also discussed.