title: Magnetic Nickel iron Electroformed Trap (MagNET): a master/replica fabrication strategy for ultra-high throughput (>100 mL h(-1)) immunomagnetic sorting.
abstract: Microfluidic devices can sort immunomagnetically labeled cells with sensitivity and specificity much greater than that of conventional methods, primarily because the size of microfluidic channels and micro-scale magnets can be matched to that of individual cells. However, these small feature sizes come at the expense of limited throughput (ϕ < 5 mL h(-1)) and susceptibility to clogging, which have hindered current microfluidic technology from processing relevant volumes of clinical samples, e.g. V > 10 mL whole blood. Here, we report a new approach to micromagnetic sorting that can achieve highly specific cell separation in unprocessed complex samples at a throughput (ϕ > 100 mL h(-1)) 100× greater than that of conventional microfluidics. To achieve this goal, we have devised a new approach to micromagnetic sorting, the magnetic nickel iron electroformed trap (MagNET), which enables high flow rates by having millions of micromagnetic traps operate in parallel. Our design rotates the conventional microfluidic approach by 90° to form magnetic traps at the edges of pores instead of in channels, enabling millions of the magnetic traps to be incorporated into a centimeter sized device. Unlike previous work, where magnetic structures were defined using conventional microfabrication, we take inspiration from soft lithography and create a master from which many replica electroformed magnetic micropore devices can be economically manufactured. These free-standing 12 μm thick permalloy (Ni80Fe20) films contain micropores of arbitrary shape and position, allowing the device to be tailored for maximal capture efficiency and throughput. We demonstrate MagNET's capabilities by fabricating devices with both circular and rectangular pores and use these devices to rapidly (ϕ = 180 mL h(-1)) and specifically sort rare tumor cells from white blood cells.
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. issadore@seas.upenn.edu.
authors.forename: Jina
authors.initials: J
authors.lastname: Ko
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. issadore@seas.upenn.edu.
authors.forename: Venkata
authors.initials: V
authors.lastname: Yelleswarapu
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. issadore@seas.upenn.edu.
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. issadore@seas.upenn.edu.
authors.forename: Nishal
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. issadore@seas.upenn.edu and Department of Electrical and Systems Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: David
authors.initials: D
authors.lastname: Issadore
mesh_terms: D045744:Cell Line, Tumor; D004867:Equipment Design; D057166:High-Throughput Screening Assays / Q000295:instrumentation*; D006801:Humans; D018189:Immunomagnetic Separation / Q000295:instrumentation*; D007501:Iron; D019169:Jurkat Cells; D060328:Magnetic Phenomena; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009369:Neoplasms / Q000097:blood / Q000473:pathology*; D009532:Nickel
chemical_list: D009532:Nickel; D007501:Iron