Multitarget magnetic activated cell sorter

Abstract

Magnetic selection allows high-throughput sorting of target cells based on surface markers, and it is extensively used in biotechnology for a wide range of applications from in vitro diagnostics to cell-based therapies. However, existing methods can only perform separation based on a single parameter (i.e., the presence or absence of magnetization), and therefore, the simultaneous sorting of multiple targets at high levels of purity, recovery, and throughput remains a challenge. In this work, we present an alternative system, the multitarget magnetic activated cell sorter (MT-MACS), which makes use of microfluidics technology to achieve simultaneous spatially-addressable sorting of multiple target cell types in a continuous-flow manner. We used the MT-MACS device to purify 2 types of target cells, which had been labeled via target-specific affinity reagents with 2 different magnetic tags with distinct saturation magnetization and size. The device was engineered so that the combined effects of the hydrodynamic force produced from the laminar flow and the magnetophoretic force produced from patterned ferromagnetic structures within the microchannel result in the selective purification of the differentially labeled target cells into multiple independent outlets. We demonstrate here the capability to simultaneously sort multiple magnetic tags with >90% purity and >5,000-fold enrichment and multiple bacterial cell types with >90% purity and >500-fold enrichment at a throughput of 10 9 cells per hour.cell sorting ͉ magnetophoresis ͉ microfluidics ͉ separation

Review Article—Dielectrophoresis: Status of the theory, technology, and applications

“…Kim et al 111 employed synthetic particles as tags that were larger than the cells, a method also adopted in the immunomagnetic method. 248 The work of Markx et al 190 in creating artificial stem cell microniches is an example of how DEP can be used as a tool to address an unmet need in stem cell research and therapy. Stem cells are immature cells characterized by a varying capacity for growth and the ability to differentiate into one or more different derivatives with specialized function.…”

Integrated acoustic and magnetic separation in microfluidic channels

“…3͑b͔͒. As described previously, 13 separation of magnetic targets from acoustic targets is achieved by balancing the magnetic force F mag and the hydrodynamic drag force F hyd . Due to the fact that the Ni lines are oriented at an angle of 5°to the fluid flow, magnetic particles are selectively deflected and directed into the magnetic outlet if F mag,Ќ Ͼ F hyd,Ќ ͑Fig.…”

“…The magnetic separation was performed as previously described by Adams et al, 13 Inglis et al, 14 and Smistrup et al 17 Briefly, a set of three external NeFeB permanent magnets are used to create long-range magnetic field gradients that serve to attract all magnetic particles toward the bottom plane of the IAMS device, where large, short-range magnetic gradients are generated by microfabricated ferromagnetic structures. 13,17 We estimate the maximum time for the long-range force to move the particles to the bottom plane of the device as…”

“…This pairing of forces is especially useful because it combines label-free separation ͑acoustophoresis͒ 11 with molecular label-based separation ͑magnetophoresis͒. [12][13][14] In addition, neither separation force is significantly affected by pH, salinity, temperature, and other characteristics of the suspension medium, such that the method can be used for a wide range of cell types and samples.…”

Shrink-induced sorting using integrated nanoscale magnetic traps

“…Separation of magnetically labeled leukocytes from whole blood was demonstrated but because only weak magnetic force (pN) was exerted on the target cells, only low throughput separations were achieved. Similarly, Adams et al 16 separated multiple bacterial cell types by utilizing different sized magnetic beads with 90%-96% purity. However, this process required large sample volumes and so may not be suitable to separate low volumes.…”