Removal of malaria-infected red blood cells using magnetic cell separators: A computational study

doi:10.1016/J.AMC.2011.12.057

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Removal of malaria-infected red blood cells using magnetic cell separators: A computational study

Journal Article•DOI•

Removal of malaria-infected red blood cells using magnetic cell separators: A computational study

Jeongho Kim¹, Mehrdad Massoudi², James F. Antaki¹, Alberto Gandini¹•Institutions (2)

Carnegie Mellon University¹, United States Department of Energy²

15 Feb 2012-Applied Mathematics and Computation (NIH Public Access)-Vol. 218, Iss: 12, pp 6841-6850

TL;DR: This paper model the malaria-infected RBCs (pRBCs) as paramagnetic particles suspended in a Newtonian fluid and shows that in order to achieve a capture efficiency of 99% for the pR BCs it is required to have a longer length than 80 mm; this implies that in principle, using optimization techniques the length could be adjusted, i.e., shortened to achieve 99% capture efficiency.

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About: This article is published in Applied Mathematics and Computation.The article was published on 2012-02-15 and is currently open access. It has received 36 citations till now.

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Journal Article•DOI•

Particle separation and sorting in microfluidic devices: a review

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P. Sajeesh¹, Ashis Kumar Sen¹•Institutions (1)

Indian Institute of Technology Madras¹

01 Jul 2014-Microfluidics and Nanofluidics

TL;DR: This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details, the working principles are explained in detail, and performances of the devices are discussed.

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Abstract: Separation and sorting of micron-sized particles has great importance in diagnostics, chemical and biological analyses, food and chemical processing and environmental assessment. By employing the unique characteristics of microscale flow phenomena, various techniques have been established for fast and accurate separation and sorting of microparticles in a continuous manner. The advancements in microfluidics enable sorting technologies that combine the benefits of continuous operation with small-sized scale suitable for manipulation and probing of individual particles or cells. Microfluidic sorting platforms require smaller sample volume, which has several benefits in terms of reduced cost of reagents, analysis time and less invasiveness to patients for sample extraction. Additionally, smaller size of device together with lower fabrication cost allows massive parallelization, which makes high-throughput sorting possible. Both passive and active separation and sorting techniques have been reported in literature. Passive techniques utilize the interaction between particles, flow field and the channel structure and do not require external fields. On the other hand, active techniques make use of external fields in various forms but offer better performance. This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details. The working principles are explained in detail, and performances of the devices are discussed.

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613 citations

Journal Article•DOI•

Numerical Simulation of Flowing Blood Cells

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Jonathan B. Freund¹•Institutions (1)

University of Illinois at Urbana–Champaign¹

03 Jan 2014-Annual Review of Fluid Mechanics

TL;DR: Numerical simulation techniques that provide a realistic description of cell-scale blood flow by explicitly representing its coupled fluid and solid mechanics are motivated and reviewed.

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Abstract: The cellular detail of blood is an essential factor in its flow, especially in vessels or devices with size comparable to that of its suspended cells. This article motivates and reviews numerical simulation techniques that provide a realistic description of cell-scale blood flow by explicitly representing its coupled fluid and solid mechanics. Red blood cells are the principal focus because of their importance and because of their remarkable deformability, which presents particular simulation challenges. Such simulations must couple discretizations of the large-deformation elasticity of the cells with the viscous flow mechanics of the suspension. The Reynolds numbers are low, so the effectively linear fluid mechanics is amenable to a wide range of simulation methods, although the constitutive models and geometric factors of the coupled system introduce challenging nonlinearity. Particular emphasis is given to the relative merits of several fundamentally different simulation methods. The detailed description provided by such simulations is invaluable for advancing our scientific understanding of blood flow, and their ultimate impact will be in the design of biomedical tools and interventions.

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281 citations

Cites background from "Removal of malaria-infected red blo..."

...…recently reported devices are designed to separate blood plasma from small samples (Homsy et al. 2012), identify and remove malaria-infected cells (Kim et al. 2012), supplant current large-scale and expensive technology to perform complete blood counts (Han et al. 2012, Layton et al. 2012), and…...
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Journal Article•DOI•

Fundamentals and application of magnetic particles in cell isolation and enrichment: a review

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Brian D. Plouffe¹, Shashi K. Murthy¹, Laura H. Lewis¹•Institutions (1)

Northeastern University¹

01 Jan 2015-Reports on Progress in Physics

TL;DR: The contribution of cell separation to biomedical research and medicine is highlighted and modern cell-separation methods are detailed, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles.

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Abstract: Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell-separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell-separation systems.

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260 citations

Journal Article•DOI•

Malarial hemozoin: from target to tool.

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Lorena M. Coronado¹, Christopher T. Nadovich², Carmenza Spadafora•Institutions (2)

Acharya Nagarjuna University¹, Clarkson University²

01 Jun 2014-Biochimica et Biophysica Acta

TL;DR: The importance and peculiarities of this biocrystal have given researchers a cause to consider it as a target for new antimalarials and to use it through unconventional approaches for diagnostics and therapeutics against the disease.

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188 citations

Journal Article•DOI•

Design of microfluidic channels for magnetic separation of malaria-infected red blood cells

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Wei-Tao Wu¹, Andrea Blue Martin¹, Alberto Gandini¹, Nadine Aubry², Mehrdad Massoudi³, James F. Antaki¹ - Show less +2 more•Institutions (3)

Carnegie Mellon University¹, Northeastern University², United States Department of Energy³

02 Feb 2016-Microfluidics and Nanofluidics

TL;DR: This study investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest, and compared the efficacy of various geometries upon the stratification efficiency of the pRBCs.

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Abstract: This study is motivated by the development of a blood cell filtration device for removal of malaria-infected, parasitized red blood cells (pRBCs). The blood was modeled as a multi-component fluid using the computational fluid dynamics discrete element method (CFD-DEM), wherein plasma was treated as a Newtonian fluid and the red blood cells (RBCs) were modeled as soft-sphere solid particles which move under the influence of drag, collisions with other RBCs, and a magnetic force. The CFD-DEM model was first validated by a comparison with experimental data from Han and Frazier (Lab Chip 6:265–273, 2006) involving a microfluidic magnetophoretic separator for paramagnetic deoxygenated blood cells. The computational model was then applied to a parametric study of a parallel-plate separator having hematocrit of 40 % with 10 % of the RBCs as pRBCs. Specifically, we investigated the hypothesis of introducing an upstream constriction to the channel to divert the magnetic cells within the near-wall layer where the magnetic force is greatest. Simulations compared the efficacy of various geometries upon the stratification efficiency of the pRBCs. For a channel with nominal height of 100 µm, the addition of an upstream constriction of 80 % improved the proportion of pRBCs retained adjacent to the magnetic wall (separation efficiency) by almost twofold, from 26 to 49 %. Further addition of a downstream diffuser reduced remixing and hence improved separation efficiency to 72 %. The constriction introduced a greater pressure drop (from 17 to 495 Pa), which should be considered when scaling up this design for a clinical-sized system. Overall, the advantages of this design include its ability to accommodate physiological hematocrit and high throughput, which is critical for clinical implementation as a blood-filtration system.

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100 citations

Cites background or methods from "Removal of malaria-infected red blo..."

...…( χrbc − χp ) Vrbca 2H0 ( Ms 2H0 a2 + ( a+ y ′ )2 ) ( a+ y ′ )5 e y ′ Microfluid Nanofluid (2016) 20:41 1 3 41 Page 6 of 11 to ring-stage malaria (Hackett et al. 2009; Kim et al. 2012); approximately 2.5 × less than deoxyhemoglobin RBCs (χdeoxyRBC = −3.8e−6) used in the Han et al.’s experiment....
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...to ring-stage malaria (Hackett et al. 2009; Kim et al. 2012); approximately 2....
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...This has motivated the development of a magnetic apheresis (mPharesis™) system to continuously purify a patient’s blood, much like a dialyzer (Kim et al. 2012; Gandini et al. 2013) (see Fig....
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...The engineering challenge is to optimize the efficiency of this magnetophoretic separator to maintain the overall size of the system within the desired envelope and limit the treatment time under 4 h (Kim et al. 2012)....
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...a Blood inlet, b Bleed slit, c Return outlet (Kim et al. 2012) Fig....
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References

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Introduction to Magnetic Materials

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B. D. Cullity, C. D. Graham

01 Jun 1972

TL;DR: In this paper, the authors present materials at the practical rather than theoretical level, allowing for a physical, quantitative, measurement-based understanding of magnetism among readers, be they professional engineers or graduate-level students.

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Abstract: Introduction to Magnetic Materials, 2nd Edition covers the basics of magnetic quantities, magnetic devices, and materials used in practice. While retaining much of the original, this revision now covers SQUID and alternating gradient magnetometers, magnetic force microscope, Kerr effect, amorphous alloys, rare-earth magnets, SI Units alongside cgs units, and other up-to-date topics. In addition, the authors have added an entirely new chapter on information materials. The text presents materials at the practical rather than theoretical level, allowing for a physical, quantitative, measurement-based understanding of magnetism among readers, be they professional engineers or graduate-level students.

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6,573 citations

"Removal of malaria-infected red blo..." refers background in this paper

...Its susceptibility is positive and large, which changes with the magnetic field H [67]....
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Low Reynolds number hydrodynamics

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John Happel, Howard Brenner

01 Jan 1965

TL;DR: Low Reynolds number flow theory finds wide application in such diverse fields as sedimentation, fluidization, particle-size classification, dust and mist collection, filtration, centrifugation, polymer and suspension rheology, and a host of other disciplines.

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Abstract: Low Reynolds number flow theory finds wide application in such diverse fields as sedimentation, fluidization, particle-size classification, dust and mist collection, filtration, centrifugation, polymer and suspension rheology, flow through porous media, colloid science, aerosol and hydrosal technology, lubrication theory, blood flow, Brownian motion, geophysics, meteorology, and a host of other disciplines. This text provides a comprehensive and detailed account of the physical and mathematical principles underlying such phenomena, heretofore available only in the original literature.

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4,648 citations

"Removal of malaria-infected red blo..." refers background in this paper

...These velocity gradients correspond to the physical effect known as Faxen forces [46]....
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Journal Article•DOI•

Equation of motion for a small rigid sphere in a nonuniform flow

[...]

Martin R. Maxey¹, James J. Riley•Institutions (1)

Brown University¹

01 Apr 1983-Physics of Fluids

TL;DR: In this paper, the forces on a small rigid sphere in a nonuniform flow are considered from first prinicples in order to resolve the errors in Tchen's equation and the subsequent modified versions that have since appeared.

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Abstract: The forces on a small rigid sphere in a nonuniform flow are considered from first prinicples in order to resolve the errors in Tchen’s equation and the subsequent modified versions that have since appeared. Forces from the undisturbed flow and the disturbance flow created by the presence of the sphere are treated separately. Proper account is taken of the effect of spatial variations of the undisturbed flow on both forces. In particular the appropriate Faxen correction for unsteady Stokes flow is derived and included as part of the consistent approximation for the equation of motion.

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3,130 citations

"Removal of malaria-infected red blo..." refers methods in this paper

...Maxey and Riley [45], based on an analysis similar to that of Buevich, proposed the following equation for the force on a sphere in a nonuniform flow: mp dvp dt ¼ þmf Dvf Dt YðtÞ 1 2 mf d dt vpðtÞ vf ½YðtÞ; t 1 10 a2r2vf YðtÞ 6palf vpðtÞ vf ½YðtÞ; t 1 6 a2r2vf YðtÞ þ 6pa2lf Z t 0 ds d ds vpðsÞ vf ½YðsÞ; s 16 a2r 2vf YðsÞ n o ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi pmf ðt sÞ p þ ðmp mf Þg: ð3Þ It is noted that the inclusion of velocity gradients in their analysis results in modifications to the virtual mass, Stokes drag, and Basset history terms in order to account for the effect of a nonuniform flow field....
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...Maxey and Riley [45], based on an analysis similar to that of Buevich, proposed the following equation for the force on a sphere in a nonuniform flow:...
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Journal Article•DOI•

The lift on a small sphere in a slow shear flow

[...]

Philip Geoffrey Saffman¹•Institutions (1)

California Institute of Technology¹

01 Jun 1965-Journal of Fluid Mechanics

TL;DR: In this article, it was shown that a sphere moving through a very viscous liquid with velocity V relative to a uniform simple shear, the translation velocity being parallel to the streamlines and measured relative to streamline through the centre, experiences a lift force 81·2μVa2k½/v½ + smaller terms perpendicular to the flow direction, which acts to deflect the particle towards the streamline moving in the direction opposite to V.

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Abstract: It is shown that a sphere moving through a very viscous liquid with velocity V relative to a uniform simple shear, the translation velocity being parallel to the streamlines and measured relative to the streamline through the centre, experiences a lift force 81·2μVa2k½/v½ + smaller terms perpendicular to the flow direction, which acts to deflect the particle towards the streamlines moving in the direction opposite to V. Here, a denotes the radius of the sphere, κ the magnitude of the velocity gradient, and μ and v the viscosity and kinematic viscosity, respectively. The relevance of the result to the observations by Segree & Silberberg (1962) of small spheres in Poiseuille flow is discussed briefly. Comments are also made about the problem of a sphere in a parabolic velocity profile and the functional dependence of the lift upon the parameters is obtained.

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2,912 citations

"Removal of malaria-infected red blo..." refers background or result in this paper

...Saffman [53,54] deduces that, since experimental results contradicted this conclusion, inertial effects must be involved....
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...The Saffman lift force is normal to the slip vector and the spin vector of the particle....
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...A generalized form of the Saffman shear lift force was proposed by Drew [62], Ahmadi [63], McTigue et al. [64]....
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...3 2 pd2lf Z t 0 d ds vp vf d 2 24r 2vf ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi pmf ðt sÞ p dsþ Kpd2ðqf lf Þ1=2Df 3ðDf : Df Þ1=4 ðvf vpÞ þ ðmp mf Þg; ð4Þ where as before the subscripts f and p denote the fluid and the particle, respectively; v is the velocity vector, t is time, lf is the dynamic viscosity, tf is the kinematic viscosity, m is the mass (m ¼ p6 d 3 pq), q is the density, d is the particle diameter (=2a), K = 2.594 is the constant coefficient of Saffman lift force, Df ¼ 12 ½rvf þ ðrvf Þ T , the time derivate for the moving particle is dvp dt ¼ @vp @t þ vp @vp @x , the fluid acceleration is defined as Dvf Dt ¼ @vf @t þ vf @vf @x , and xp ¼ xpex þ ypey....
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...(4) reduces to the lift force in a uniform shear field provided by Saffman [53,54]....
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Journal Article•DOI•

Magnetism and microfluidics

[...]

Nicole Pamme¹•Institutions (1)

National Institute for Materials Science¹

20 Dec 2006-Lab on a Chip

TL;DR: The aim of this review is to introduce and discuss the various developments within the field of magnetism and microfluidics.

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Abstract: Magnetic forces are now being utilised in an amazing variety of microfluidic applications. Magnetohydrodynamic flow has been applied to the pumping of fluids through microchannels. Magnetic materials such as ferrofluids or magnetically doped PDMS have been used as valves. Magnetic microparticles have been employed for mixing of fluid streams. Magnetic particles have also been used as solid supports for bioreactions in microchannels. Trapping and transport of single cells are being investigated and recently, advances have been made towards the detection of magnetic material on-chip. The aim of this review is to introduce and discuss the various developments within the field of magnetism and microfluidics.

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1,136 citations