1. Field of the Invention
This invention relates to a magnetic sensor for the detection of small particles magnetized by an external magnetic field, particularly to such a sensor that utilizes an external field applied in a direction perpendicular to the sensor plane.
2. Description of the Related Art
Magnetic sensors have been shown as capable of detecting the presence of specific chemical and biological molecules when such molecules are a part of a fluid mixture that includes many other types of molecules. The method underlying such magnetic detection of molecules requires that labels, comprising small magnetic (or magnetizable) particles, be attached to the specific molecules in the mixture that are of interest. The magnetic particles used as such labels may have ferromagnetic, ferrimagnetic, paramagnetic or superparamagnetic properties. Particles with ferromagnetic or ferrimagnetic characteristics have intrinsic magnetic moments, whereas particles with paramagnetic or superparamagnetic properties acquire an induced magnetic moment when placed in an external magnetic field. Irrespective of the magnetic characteristics of the label, the particle's detection system typically includes a magnetic field which serves to either magnetize or orient the particles. The magnetic field may be produced by an external source, such as a permanent magnet or an electromagnet, or it may be generated locally using an electrical current flowing through a conductor of the appropriate geometry that is an integrated component of the sensor configuration. In either case, the local magnetic stray field of the attached particle would be used to generate a detectable signal from the magnetic sensor. The present invention will be concerned with particles that require an applied magnetic field to magnetize them so that they will produce a local stray field suitable for detection by the sensor apparatus. In particular, the invention is concerned with embodiments where the magnetic sensing apparatus utilizes the in-plane (i.e., the plane of the substrate confining the labeled molecules) component of this stray field to produce a signal indicative of the presence of the magnetic label particle
The magnetizable particles used as labels (to be called, simply, “magnetic labels” in the following) are attached to molecules by coating them with a chemical substance or biological species that binds to those molecules. Then, a surface is provided on which there has been affixed receptor sites (e.g., specific molecules) to which only the molecules of interest will bond. After the mixture has been in contact with the surface so that the molecules of interest have bonded to the receptor sites, the surface is flushed in some manner to remove all unbonded molecules. Because the bonded target molecules are equipped with the attached magnetic labels, it is only necessary to detect (and count) the magnetic labels to be able, at the same time, to assess the number of captured target molecules. Thus, the magnetic particles are simply “labels,” which can be easily detected and counted once the molecules of interest have been captured by chemical bonding to the receptor sites on the surface. The technological issue, then, is to provide an effective method of detecting these small magnetic labels, since their detection is tantamount to detection of the target molecules.
One prior art method of detecting small magnetic labels affixed to molecules bonded to receptor sites is to position a means of sensing a magnetic field beneath the receptor sites. Such a sensing means could be a device that makes use of the magneto-resistive effect. These devices are already employed as read-heads to sense local fields from a magnetic recording medium. In other configurations, they are used to sense the local fields produced by an MRAM storage element in a magnetic memory array. In a preferred embodiment of this invention, the sensing device can be positioned beneath the substrate surface on which the receptor sites have been placed.
FIG. 1 is a highly schematic diagram (typical of the prior art methodology) showing a magnetic label (10) covered with receptor sites (20), with four identical sites being shown for exemplary purposes. Each of these identical sites is specific to bonding with a target molecule (30) (shown shaded) which is shown as already being bonded to one of the sites. Note that “bonding” is schematically indicated by the insertion of a shaped end of the molecule (30) into a correspondingly shaped opening into the receptor site. A substrate (40) is covered with another set of identical receptor sites (50) that are also specific to target molecule (30) and those sites may, in general, be different from the sites that bond the magnetic label to the molecule. The target molecule (30) is also shown bonded, at its other end, to one of the receptor sites (50) on the surface. Thus, the magnetic label (10), is held above the substrate (40), by means of the molecule (30) that serves as a doubly bonded link.
FIG. 2 schematically shows a prior art GMR sensor (60) and associated circuitry that is positioned beneath the substrate (40) of FIG. 1. Such prior art is also taught by Baselt (U.S. Pat. No. 5,981,297). Improvements on such prior art, which are not shown here, are taught by Shiaa et al. (US Published Patent Application 2006/0291108).
For clarity, the receptor sites on the substrate shown in FIG. 1 are not shown in FIG. 2. As shown schematically in the cross-sectional view of FIG. 2, the prior art GMR sensor (60) is preferably in the form of a laminated thin film stripe that includes a magnetically free layer (61) and a magnetically pinned layer (63) separated by a thin, non-magnetic but electrically conducting spacer layer (62). The pinned layer is shown with a fixed magnetic moment (a single ended arrow (630)) and the free layer is shown with a variable moment (double ended arrow (610)). It should be noted that the GMR structure (60) could be replaced by a TMR (tunneling magneto resistive) element, in which case layer (62) would be a thin dielectric layer rather than a thin conducting layer. The important feature in either the GMR or TMR case is that the sensor changes its resistance in accord with the presence of an external magnetic stray field generated by the magnetic label as will be discussed below. For realism, some additional circuit elements are schematically indicated, such as source (72), drain (76) and gate (74) regions of an accessing transistor formed in a solid-state (e.g., Si) substrate (70) that would allow the sensor (60) to be selected for measuring purposes, through a conducting via (65), by means of currents in conducting lines (200) and (85).
The properties of the sensor (either GMR or TMR) causes it to act essentially as a resistor whose resistance depends on the relative orientation of the magnetic moments of the free (610) and pinned (630) layers, with a low resistance value being associated with alignment of the moments and a high value being associated with anti-alignment.
Referring to FIG. 3, there is shown a schematic illustration of a portion of an array of prior art sensors of the type shown singly in FIG. 2, in which pairs (two pairs being shown) of sensors (60a), (60b) and (60c), (60d) are formed beneath an upper substrate (40) on which molecules will be bound for identification purposes. The sensors are accessed by current carrying lines (200a), (200b) (85a) and (200c), (200d), (85b). Typically, the sensors will be separated by insulation layers (400) and will be formed on a substrate (70) that is suitable for the fabrication of the various types of solid-state electronic circuitry, such as a region forming an accessing transistor (72). This array is highly schematic and is shown for exemplary purposes only. Other configurations could equally well link sensors of the type shown in FIG. 2 into a multi-sensor array.
Referring now to schematic FIG. 4, there is shown again the single prior art sensor of FIG. 2, now with a magnetic label (10) positioned above it. It is understood that the label is attached by a molecule (not shown) to a receptor site (not shown) on the upper substrate (40) as shown in FIG. 1. An applied magnetic field H (450), which could be static or dynamic, is represented by a single vertical arrow directed downward and substantially perpendicular to the substrate (40). The magnetic field, H, has induced a magnetic moment, m, (500) in the magnetic label (10) that is substantially co-directional with H. The magnetic moment generates a magnetic stray field, B, (550) typically of a magnetic dipole shape, that is here schematically represented by curved field lines (550) external to the particle. As indicated in the drawing, stray field B has a component that is parallel to the substrate plane (40) (hereinafter referred to as an “in-plane” component) and is also parallel to the free layer (61) of the sensor (60). It is this in-plane component that is responsible for producing variations (e.g., vector rotations) of the magnetic moment (610) of the sensor's free layer and, thereby, producing a measurable change in the resistance of the sensor that allows the presence of the magnetic label to be detected. Although the applied magnetic field, H, may be substantially more intense than B, its presence does not affect the free layer magnetic moment if it is precisely perpendicular to the plane of the free layer. If, however, the applied magnetic field, H, were not perpendicular, its in-plane component could significantly perturb the effects of B, and thereby adversely affect the accuracy of the sensor. The presence of an in-plane component can also adversely affect the signal-to-noise ratio of such a sensor, as is noted by Kahlman et al. (U.S. Pat. No. 7,250,759) who also teaches methods for changing the external magnetic field and, in combination with noise canceling circuitry, thereby improving the performance of a sensor. It is to detecting the presence of magnetic labels while mitigating the adverse effects of in-plane components of an applied magnetic field that this invention is directed, as indicated in the objects set forth below.