Magnetic Bead-based Biosensor

Magnetoresistive biosensor based on the detection of magnetic labels on a chip containing magnetoresistive sensing elements such as GMR,spin-valve and tunnel junction sensors, are drawing much attention for the potential applications in molecule recognition. Micromagnetic simulation is a powerful technique to optimally design the sensing elements.

Companies are designing and fabricating magnetic microsensors optimized for the detection of magnetic beads. At present, we are using sensors based on the planar Hall effect, which utilizes anisotropic magnetoresistance in Hall geometry. These sensors are sensitive to the field in the plane of the sensor.

The output voltage from the magnetic sensor is related to the total average magnetic field acting on the sensor. When beads are present on the sensor, this field is changed compared to when the beads are not there. This change is related to the bead coverage of the sensor.

The sensor and the beads are functionalized such that they bind specifically to the species to be detected and form a sensor-species-bead sandwich. Ideally, beads will only be bound to the sensor when this species is present in the sample. Hence, the species is detected by detecting the presence of the beads.

Convergence between nanotechnology and biomedical applications over the past few years has led to focus in the development of miniature total analysis systems to speedily identify the smallest traces of e.g. food pathogens or bioweapons. Bioassays involving pL of reagents can at present be done in microarrays, which identify hybridization of a particular fluorescently labelled biochemical probe to the unknown biomolecule by observation of a spatially resolved fluorescence signal. However, it is difficult to both automate and extend the detection capability; the selectivity of microarrays also depends on the concentration of molecule to be analyzed in the sample. Therefore, very recent efforts have concentrated on performing assays in microfluidic flow cells using combinatorial libraries of micron-sized magnetic beads functionalised with biochemical probes. This method allows flexible, automated, high-throughput analysis, whose detection capabilities can be extended simply by increasing the size of the library rather than the number of sites in the microarray. This is such a great motivation for the development of highly sensitive, robust, miniaturized magnetic sensors which can be integrated into microfluidic systems.

This effort builds on previous work by using mesoscopic ferromagnetic rings to detect such beads. Rings are ideal for this application due to their extremely repeatable and abrupt switching between only four possible stable magnetisation states - the flux-closed "vortex" states of opposite circulations and the "onion" states which contain a pair of head-to-head or tail-to-tail domain walls. Furthermore, the strong dependence of their switching fields on geometric parameters such as thickness, linewidth and external diameter allows rings to be adjusted to react only to specific field ranges.

If a magnetic bead is positioned above such a ring in an applied external magnetic field, it would act as a magnetic dipole and its stray field will oppose and partially cancel the external field in an area similar to its own cross-section projected onto the plane of the ring. This reduces the field experienced by the ring; by controlling the bead-ring separation and the bead magnetic moment, the switching of the ring can be prevented and the corresponding resistance signal read out. Please see the schematic below.

a 2 micron diameter circular multilayer ring	Schematic of bead detection

Controlling the distance of the bead relative to the ring can be achieved by integrating the sensors into a microfluidic channel into which the beads are introduced in suspension. Thus,magnetic beads can be transported and positioned over the ring by applied hydrodynamic forces or electromagnetic field gradients generated by lithographically defined current lines inside or flanking the channel.