Magnetic force-based multiplexed immunoassay using superparamagnetic nanoparticles in microfluidic channel

Abstract

This paper describes a novel microfluidic immunoassay utilizing binding of superparamagnetic nanoparticles to beads and deflection of these beads in a magnetic field as the signal for measuring the presence of analyte. The superparamagnetic 50 nm nanoparticles and fluorescent 1 microm polystyrene beads are immobilized with specific antibodies. When target analytes react with the polystyrene beads and superparamagnetic nanoparticles simultaneously, the superparamagnetic nanoparticles can be attached onto the microbeads by the antigen-antibody complex. In the poly(dimethylsiloxane)(PDMS) microfluidic channel, only the microbeads conjugated with superparamagnetic nanoparticles by analytes consequently move to the high gradient magnetic fields under the specific applied magnetic field. In this study, the magnetic force-based microfluidic immunoassay is successfully applied to detect the rabbit IgG and mouse IgG as model analytes. The lowest concentration of rabbit IgG and mouse IgG measured over the background is 244 pg mL(-1) and 15.6 ng mL(-1), respectively. The velocities of microbeads conjugated with superparamagnetic nanoparticles are demonstrated by magnetic field gradients in microfluidic channels and compared with the calculated magnetic field gradients. Moreover, dual analyte detection in a single reaction is also performed by the fluorescent encoded microbeads in the microfluidic device. Detection range and lower detection limit can be controlled by the microbeads concentration and the higher magnetic field gradient.

Computational design optimization for microfluidic magnetophoresis

“…In addition, the design presented here accounts for drag forces experienced by cells tagged with hundreds of magnetic beads. This approach is more realistic for continuousflow cell separation compared to that described by prior theoretical/computational models that only consider the manipulation of magnetic micro-or nanoparticles in the absence of cell attachment, 30,24,32 as cells are generally much larger in size relative to the particles. The device model described here also introduces a new and unique sheath-based design in which a system of two electromagnets acts cooperatively to displace cells within a central microfluidic channel.…”

“…In addition to addressing biohazard considerations, this arrangement will significantly reduce cost associated with device manufacture and implementation. In contrast to prior models of continuous-flow magnetic-microfluidic separation devices, 30,31,24,32 the specific advance articulated in this paper is the development and implementation of a realistic rational design based on practical experimental constraints and desired need for a microfluidic system capable of delivering both high efficiency and high purity. The described approach directly accounts for variations in key parameters within the cells, tagging particles, and device and addresses several key parameters, which may advance this device to clinical and bench-top applications.…”

“…The described approach directly accounts for variations in key parameters within the cells, tagging particles, and device and addresses several key parameters, which may advance this device to clinical and bench-top applications. Although many modeling approaches have been well established in literature, 30,31,24,32 these examples fail to address all of the requirements of a clinically usable cell separation platform. The magnet-based cell separation device presented here aims to incorporate clinical diagnostic considerations ab initio by constraining the device microfluidic channel dimensions to a practical scale ͑i.e., that of a microscope slide͒ and incorporating disposable and nondisposable components ͑fluidic and magnetic parts, respectively͒ in the device as a means of reducing cost.…”

“…The magnet-based cell separation device presented here aims to incorporate clinical diagnostic considerations ab initio by constraining the device microfluidic channel dimensions to a practical scale ͑i.e., that of a microscope slide͒ and incorporating disposable and nondisposable components ͑fluidic and magnetic parts, respectively͒ in the device as a means of reducing cost. Furthermore, the incorporation of a tunable electromagnet ͑relative to state-of-theart on-chip designs that employ permanent magnets 30,32 ͒ maximizes versatility in addition to reducing device cost. In addition, the design presented here accounts for drag forces experienced by cells tagged with hundreds of magnetic beads.…”

Ultra‐Specific Isolation of Circulating Tumor Cells Enables Rare‐Cell RNA Profiling

“…The magnetic sorter has three inlets consisting of two outer buffer streams and one middle sample stream that flow in a 250 μm wide channel and allows for further continuous on‐chip cell sorting 14. Confining the sample stream in this manner ultimately provides efficient magnetized CTC sorting from contaminating cells by ensuring that only magnetized cells are attracted into the collection outlet.…”