Lab-on-a-Chip Magneto-Immunoassays: How to Ensure Contact between Superparamagnetic Beads and the Sensor Surface

Abstract

Lab-on-a-chip immuno assays utilizing superparamagnetic beads as labels suffer from the fact that the majority of beads pass the sensing area without contacting the sensor surface. Different solutions, employing magnetic forces, ultrasonic standing waves, or hydrodynamic effects have been found over the past decades. The first category uses magnetic forces, created by on-chip conducting lines to attract beads towards the sensor surface. Modifications of the magnetic landscape allow for additional transport and separation of different bead species. The hydrodynamic approach uses changes in the channel geometry to enhance the capture volume. In acoustofluidics, ultrasonic standing waves force µm-sized particles onto a surface through radiation forces. As these approaches have their disadvantages, a new sensor concept that circumvents these problems is suggested. This concept is based on the granular giant magnetoresistance (GMR) effect that can be found in gels containing magnetic nanoparticles. The proposed design could be realized in the shape of paper-based test strips printed with gel-based GMR sensors.

High Sensitivity Differential Giant Magnetoresistance (GMR) Based Sensor for Non-Contacting DC/AC Current Measurement

“…Finally, the differential sensing method presented in this article can be used for other specific applications requiring a high degree of sensitivity. As measuring low currents implies accurate detection of magnetic fields smaller than 0.5 G, some of the results presented in this paper will be used to develop a high sensitivity detection setup of magnetic nanoparticles (MNPs) used to label biomolecules in lab-on-a-chip (LOC) applications [33][34][35][36][37]. As we showed by micromagnetic simulations [35,36] and experiments [34], to achieve a large signal from MNPs, they must be polarized in quite a large magnetic field that can saturate the spintronic sensors.…”

Rapid separation of bacteria from blood—review and outlook

“…They can be purchased with “ready‐to‐conjugate” surface chemistry, so they can be easily attached to biomolecules . One challenge with magnetic beads is that a single bead, while superparamagnetic may still not generate sufficient force in the magnetic field to quickly move to a capture surface or region because of the very strong viscous drag forces . Thus hundreds of magnetic particles may be required to “pull down” the bacteria in the face of strong hydrodynamic forces .…”

Giant Magnetoresistance: Basic Concepts, Microstructure, Magnetic Interactions and Applications

“…Usually, this is achieved by embedding superparamagnetic magnetite nanoparticles in a polymer matrix. Chemically synthesized FeCo nanoparticles are good candidates even for single molecule detection as well, due to their superior saturation magnetization and, therefore, larger stray fields [ 64 ]; (2) the interface between chemistry and biology has to be fitted for each application, to allow a specific functionalization of the marker and sensor surface, e.g., for the detection of biotin-labeled DNA, streptavidin coated particles can be used [ 65 , 66 ]; (3) the GMR sensors have to be incorporated in fluidic environments, which enable the magnetic markers to pass the sensor surfaces at close distances to ensure a binding onto the surface within an acceptable time scale [ 67 ]. Due to the magnetic nature of the markers, magnetic attraction forces, created e.g., by on-chip conducting lines or magnetically structured thin films, can be employed to pull beads towards the sensors [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ].…”

“…Due to the magnetic nature of the markers, magnetic attraction forces, created e.g., by on-chip conducting lines or magnetically structured thin films, can be employed to pull beads towards the sensors [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Another way to concentrate beads on a sensing surface uses of ultrasonic standing waves inside a microfluidic channel system [ 76 , 77 ] or the microfluidic system itself can be utilized to transport beads towards the sensor surface, e.g., by designing a ramp like structure [ 67 , 78 ].…”