Increasing use is being made in biological analysis technology, medical technology and other comparable fields, of magnetic or magnetizable microparticles with sizes of less than 2 μm, for example as markers or labels for biomolecules. The problem arises in this case of detecting such-particles with the aid of magnetic field sensors. To this end, it is customary to apply an external magnetic field to which the particles react with a magnetic stray field that is to be detected.
It is known with biochips to detect magnetizable particles, which are also denoted as magnetic beads or beads, for short, with the aid of a sensor array that is arranged in the region of an analytical surface of the biochip and is formed from a number of XMR sensors. Because of the size of the individual sensors and their interconnection, it has so far been impossible to make statements on the position of a particle relative to a sensor and on the exact number of particles present in a specific area, and thereby, for example, to infer the number of molecules marked thereby.
A complex system for detecting specific biological structures is known from the publication Biosensor & Bioelectronics 14 (2000), pages 805 to 813. Use is made in this case of a matrix with n GMR sensors that are intended to detect the presence of biologically activated magnetizable particles. The matrix includes 8 arrays with 8 GMR sensors each. The individual sensors are 5 μm wide and 80 μm long. The spacing between the sensors is approximately 20 μm (grid dimension). The particles used have a diameter of 0.7 μm. The aim with this geometry is, in particular, to prevent crosstalk between individual sensors.
The influence of a particle stray field on the sensor resistance is a function of the position of the bead: in the ideal case, the field is entirely covered, whereas the field decreases rapidly at the edge of the sensor. However, the stray field cannot influence more than one sensor, otherwise, for example, an element could not display a zero signal while the neighboring ones indicate half the signal or the whole one. There is no further explanation here of an electronic system suitable for sensor evaluation.
Furthermore, the production of GMR sensor arrays is described in the Journal of Applied Physics, Vol. 93, 10, pages 6864 to 6866. The arrays have 32 or 128 elements and include sub-arrays. The spacing between the sensors is much greater than the dimensions of the sensors. The electronic system reads out the sensors in pairs (half bridge). The sensors have dimensions of 1.5 to 2 μm width and 6 μm length or 32 μm width and 2 mm length. The spacings are 5 μm or 15 μm for the narrow sensors (FIG. 1, FIG. 2) and approximately 200 μm for the wide sensors (FIG. 3). The measuring location resolution of the arrays was determined as approximately 1 mm with the aid of a structure of large area, for example by means of an ink distribution. However, there is in this case no measurement of magnetic or magnetizable microparticles. Further applications named there in addition to biotechnology are nondestructive testing technology, document testing for bank bills or credit cards, for example, or the field of position sensors.
The problem of determining the position of particles relative to the sensors and/or determining the exact number of particles in a specific area is also important for other sets of magnetic questions. In addition to the marking of objects (for example dusts, biological cells), there can also be the need to characterize magnetic microparticles directly, for example when analyzing corrosion products in oils.
USPTO Backgrounds
USPTO Backgrounds