Computational design optimization for microfluidic magnetophoresis

Abstract

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.

An Integrated Platform for Isolation, Processing, and Mass Spectrometry-based Proteomic Profiling of Rare Cells in Whole Blood*

“…S4A). Based on our comparative analysis of the above samples, we estimated that only ϳ3% of proteins identified in MCF-7 cells isolated from the blood corresponded to nonspecifically bound blood proteins, which is in agreement with previous findings where Ն95% purity of isolation was observed (26). The coefficient of variation (CV) of 3% in the number of protein groups identified in the four analyses showed good reproducibility of both cell capture and analysis.…”

“…Approval from the Northeastern University Institutional Review Board was obtained for this purpose (NU IRB #: 11-07-19). The location of the interface between the injected blood and buffer was first evaluated (12,26). A Coulter counter/flow cytometer (Cell Lab Quanta™ SC; Beckman Coulter, Brea, CA) was used to count the number of target (MCF-7) cells versus native polymorphonuclear cells that were separated.…”

Simulation guided design of a microfluidic device for electrophoretic stretching of DNA

“…Influenced by this trend, numerical simulations have been gradually emerging in the design process of microfluidic devices. 1,[8][9][10] To use computer modeling as a design tool, it is necessary that the employed models are able to predict qualitatively or even quantitatively the key physical phenomena involved. For problems concerning large time and length scales, computational fluid dynamics (CFD) 11 has become a necessary tool in any serious design.…”

Geometrical optimization of microstripe arrays for microbead magnetophoresis

“…4,6,7 To obtain high throughput, magnetic forces have also been used to separate magnetic beads in a fluid flow. [8][9][10][11] Cleanroom fabrication has been used to fabricate chips with hard ferromagnetic materials in the micro regime that show a great reproducibility for purifying magnetic beads. [12][13][14] Moreover, arrays of cobalt micro-magnets in combination with a rotating external magnetic field have been used for the magnetophoretic transportation of magnetic beads, and their ability to separate beads with different magnetophoretic mobilities by tuning the frequency of the applied magnetic field has been demonstrated.…”