Quadrupole magnetic field-flow fractionation for the analysis of magnetic nanoparticles

Carpino, Francesca; Moore, Lee R.; Chalmers, Jeffrey J.; Zborowski, Maciej; Williams, P. Stephen

doi:10.1088/1742-6596/17/1/024

Cited by 13 publications

(16 citation statements)

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“…15 To overcome some of these limitations, techniques based on continuous-flow separation of magnetically tagged cell have been investigated. 16,17 These analytical tools are typically bulky and require large volumes of sample ͑Ͼ5 ml͒ for operation. 17 The advancement of MACS technology over the last 5-10 years has focused on miniaturization of the continuous-flow analysis chambers to the micron scale.…”

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confidence: 99%

“…16,17 These analytical tools are typically bulky and require large volumes of sample ͑Ͼ5 ml͒ for operation. 17 The advancement of MACS technology over the last 5-10 years has focused on miniaturization of the continuous-flow analysis chambers to the micron scale. [18][19][20][21][22][23] These microscale fluidic devices, or microfluidic channels, allow for the analysis of significantly smaller sample volumes while maintaining comparable purity of target cells within the collection suspension.…”

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Computational design optimization for microfluidic magnetophoresis

2011

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Current macro-and microfluidic approaches for the isolation of mammalian cells are limited in both efficiency and purity. In order to design a robust platform for the enumeration of a target cell population, high collection efficiencies are required. Additionally, the ability to isolate pure populations with minimal biological perturbation and efficient off-chip recovery will enable subcellular analyses of these cells for applications in personalized medicine. Here, a rational design approach for a simple and efficient device that isolates target cell populations via magnetic tagging is presented. In this work, two magnetophoretic microfluidic device designs are described, with optimized dimensions and operating conditions determined from a force balance equation that considers two dominant and opposing driving forces exerted on a magnetic-particle-tagged cell, namely, magnetic and viscous drag. Quantitative design criteria for an electromagnetic field displacement-based approach are presented, wherein target cells labeled with commercial magnetic microparticles flowing in a central sample stream are shifted laterally into a collection stream. Furthermore, the final device design is constrained to fit on standard rectangular glass coverslip ͑60 ͑L͒ ϫ 24 ͑W͒ ϫ 0.15 ͑H͒ mm 3 ͒ to accommodate small sample volume and point-of-care design considerations. The anticipated performance of the device is examined via a parametric analysis of several key variables within the model. It is observed that minimal currents ͑Ͻ500 mA͒ are required to generate magnetic fields sufficient to separate cells from the sample streams flowing at rate as high as 7 ml/h, comparable to the performance of current state-of-the-art magnet-activated cell sorting systems currently used in clinical settings. Experimental validation of the presented model illustrates that a device designed according to the derived rational optimization can effectively isolate ͑ϳ100%͒ a magnetic-particle-tagged cell population from a homogeneous suspension even in a low abundance. Overall, this design analysis provides a rational basis to select the operating conditions, including chamber and wire geometry, flow rates, and applied currents, for a magnetic-microfluidic cell separation device.

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Computational design optimization for microfluidic magnetophoresis

2011

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“…On the other hand, a helical channel has a single inlet and a single outlet, the helical path forces all particles to sample any circumferential variations in field gradient, and the approach taken for channel assembly tends to reduce variations in channel thickness. The helical channel is machined into the surface of a polyoxymethylene rod (Delrin™ from DuPont) that fits tightly into an internally polished stainless steel tube [2–4]. It is therefore self-centering throughout the length of the tube.…”

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Theory for nanoparticle retention time in the helical channel of quadrupole magnetic field-flow fractionation

Williams

Carpino

Zborowski

2009

Journal of Magnetism and Magnetic Materials

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Quadrupole magnetic field-flow fractionation (QMgFFF) is a separation and characterization technique for magnetic nanoparticles such as those used for cell labeling and for targeted drug therapy. A helical separation channel is used to efficiently exploit the quadrupole magnetic field. The fluid and sample components therefore have angular and longitudinal components to their motion in the thin annular space occupied by the helical channel. The retention ratio is defined as the ratio of the times for non retained and a retained material to pass through the channel. Equations are derived for the respective angular and longitudinal components to retention ratio. KeywordsField-flow fractionation; magnetic field-flow fractionation; MgFFF; magnetic nanoparticles; nanoparticle characterization; quadrupole magnetic field; helical channelThe field-flow fractionation (FFF) techniques are for the separation and characterization of particulate and macromolecular materials suspended or dissolved in a liquid medium. They are similar to chromatography in that different components of a small sample elute from a separation channel at different times [1]. Chromatography exploits differences in partition between mobile and stationary phases to separate sample components as they are carried along a column, but FFF separation is achieved within the flowing mobile phase and does not utilize a stationary phase. The separation channel optimally has a uniform thickness and a high aspect ratio, i.e., it is much thinner than it is broad. The fluid velocity profile is therefore parabolic, or close to parabolic, with the fastest velocity close to the center and zero velocity at the walls. The small perturbation due to the viscous drag of the side-walls may be ignored for a channel of high aspect ratio. A field of some type is applied across the channel thickness, perpendicular to the direction of fluid flow. The materials to be separated (we restrict our consideration to submicron particles in this work) interact with the field and are driven toward one of the walls, known as the accumulation wall. The resulting increase in concentration adjacent to the accumulation wall is opposed by Brownian diffusion, and dynamic steady-state distributions are approached where the concentration of each species is highest adjacent to the wall and decays exponentially away from the wall. Furthermore, the rate of exponential decay is related *Corresponding

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“…The quadrupole magnetic field-flow fractionation (QMgFFF) system has been described previously (Carpino et al 2005a(Carpino et al ,b, 2007Williams et al 2009a). The quadrupole electromagnet was designed and assembled in our laboratory.…”

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Characterization of magnetic nanoparticles using programmed quadrupole magnetic field-flow fractionation

Williams

Carpino

Zborowski

2010

Phil. Trans. R. Soc. A.

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Quadrupole magnetic field-flow fractionation is a relatively new technique for the separation and characterization of magnetic nanoparticles. Magnetic nanoparticles are often of composite nature having a magnetic component, which may be a very finely divided material, and a polymeric or other material coating that incorporates this magnetic material and stabilizes the particles in suspension. There may be other components such as antibodies on the surface for specific binding to biological cells, or chemotherapeutic drugs for magnetic drug delivery. Magnetic field-flow fractionation (MgFFF) has the potential for determining the distribution of the magnetic material among the particles in a given sample. MgFFF differs from most other forms of field-flow fractionation in that the magnetic field that brings about particle separation induces magnetic dipole moments in the nanoparticles, and these potentially can interact with one another and perturb the separation. This aspect is examined in the present work. Samples of magnetic nanoparticles were analysed under different experimental conditions to determine the sensitivity of the method to variation of conditions. The results are shown to be consistent and insensitive to conditions, although magnetite content appeared to be somewhat higher than expected.

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Quadrupole magnetic field-flow fractionation for the analysis of magnetic nanoparticles

Cited by 13 publications

References 10 publications

Computational design optimization for microfluidic magnetophoresis

Computational design optimization for microfluidic magnetophoresis

Theory for nanoparticle retention time in the helical channel of quadrupole magnetic field-flow fractionation

Characterization of magnetic nanoparticles using programmed quadrupole magnetic field-flow fractionation

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