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A ferromagnetic thin-film based magnetic field detection system used for detecting the presence of selected molecular species. A magnetic field sensor supported on a substrate has a binding molecule layer positioned on a side thereof capable of selectively binding to the selected molecular species. The magnetic field sensor can be substantially covered by an electrical insulating layer having a recess therein adjacent to the sensor in which the binding molecule layer is provided. An electrical interconnection conductor can be supported on the substrate at least in part between the sensor and the substrate, and is electrically connected to the sensor. The magnetic field sensor can be provided in a bridge circuit, and can be formed by a number of interconnected individual sensors.
1. A ferromagnetic thin-film based magnetic field detection system, said system comprising:
a substrate;
a magnetic field sensor supported on said substrate having a pair of terminating regions between which occurs an electrical resistance having magnitudes dependent on magnetic fields occurring about said magnetic field sensor;
an electrical interconnection conductor supported on said substrate at least in part between said magnetic field sensor and said substrate, and electrically connected to one of said terminating regions of said magnetic field sensor; and
a binding molecule layer positioned on that side of said magnetic field sensor opposite said substrate, said binding molecule layer selectively binds to selected molecular species.
2. The system of
3. A ferromagnetic thin-film based magnetic field detection system, said system comprising:
a substrate;
a magnetic field sensor supported on said substrate;
an electrical insulating layer substantially covering said magnetic field sensor having a recess therein adjacent to said magnetic field sensor; and
a binding molecule layer positioned in said recess, said binding molecule layer selectively binds to selected molecular species.
4. The system of
5. The system of
This application claims priority from Provisional Application No. 60/159,185, filed Oct. 13, 1999, entitled "Magnetoresistive Bead Assay".
The present invention relates to the detection of magnetizable beads and, more particularly, to detection of magnetizable beads in connection with biological and chemical assays.
Among the biomolecular detection methods used to detect selected molecules in the presence of other kinds of molecules mixed therewith are binding assays which are based on use of certain binding molecules to capture through specific chemical bondings the molecules selected for detection. Such specific bondings include polynucleic acid bondings or hybidizations involving DNA and RNA, antibody to antigen bondings, and various ligand to various receptor bondings. The detection of the selected molecules may be of primary interest in its own right, but may instead be of primary interest in indicating the presence of some other analyte molecule, species or organism.
One arrangement for implementing such a detection scheme is to provide a sensor in which the binding molecules are relatively strongly attached to a solid substrate. An assay is begun by applying a sample solution containing various kinds of molecules possibly including the molecules selected for detection to the sensor along with label molecules attached to label beads (or particles) also present in the sample solution or in a supplemental solution concurrently also applied. The binding molecules through specific bondings, or recognition events, capture the selected molecules or the label molecules attached to label beads, or both, and thereafter hold them at the corresponding capture sites, i.e. the sites of the binding molecules undergoing such a bonding.
Label molecules on label beads are needed so that the occurrence of a recognition event leads to some measurable signal to indicate that a selected molecule was found present. One kind of label bead for doing this is a paramagnetic material bead having magnetizations that depend on externally applied magnetic fields. Application of such an externally applied field forcefully draws away any unbound label beads leaving the bound label beads at the capture sites while also magnetizing those bound label beads. Magnetic field detectors at the capture sites must sense the anomalies introduced into the externally applied field by the presence of bound label beads to produce the desired signals indicating the number of, and possibly the location of, such bound label beads. From this information the number of selected molecules, and kinds thereof, in the sample solution can be determined.
Such label beads can range in magnetic material composition from pure ferromagnetic material (e.g. permalloy) to small percentages of paramagnetic material encapsulated in plastic or ceramic spheres. As indicated above, such label beads are typically coated with a chemical or biological species that selectively binds to the selected molecules in an analyte of interest including DNA, RNA, viruses, bacteria, microorganisms, proteins, etc. to define the assay function, or the kind of recognition events, to be associated with that bead.
However, the label beads must typically be very small, that is, on the order of a few to tens of nanometers (nm) up to maybe a hundred or so or even up to a few microns in some instances. As a result the anomalies in an externally applied field will be very small. Thus, there is a desire for suitable magnetic field detectors for use with such beads.
The present invention provides a ferromagnetic thin-film based magnetic field detection system used for detecting the presence of selected molecular species. The system has a magnetic field sensor supported on a substrate with a binding molecule layer positioned on a side thereof capable of selectively binding to the selected molecular species. The magnetic field sensor is substantially covered by an electrical insulating layer which in some embodiments has a recess therein adjacent to the sensor in which the binding molecule layer is provided. An electrical interconnection conductor is supported on the substrate at least in part between the sensor and the substrate in some embodiments, and is electrically connected to the sensor. The magnetic field sensor can be provided in a bridge circuit, and can be formed by a number of interconnected individual sensors located adjacent to the binding molecule layer.
FIG. 1 shows a coordinate definition schematic diagram,
FIG. 2 shows a magnetizable sphere based magnetic response field schematic over a structure,
FIG. 3 shows a direction lines schematic for a magnetizable sphere in a uniform externally applied field,
FIG. 4 shows field magnitude value bands for the field of FIG. 3 at a selected plane,
FIG. 5 shows an alternative magnetizable sphere based magnetic response field schematic over a structure,
FIG. 6 shows a detector device portion embodying the present invention,
FIG. 7 shows an electrical schematic diagram providing a representation of FIG. 6,
FIGS. 8 and 9 show layer diagrams of a detector device portion embodying the present invention,
FIG. 10 shows a detector device portion embodying the present invention,
FIG. 11 shows a layer diagram of a detector device portion embodying the present invention,
FIG. 12 shows a graph having a plot representing performance of a component used with the present invention,
FIGS. 13, 14 and 15 show detector device portions embodying the present invention,
FIGS. 16 and 17 show layer diagrams of a detector device portion embodying the present invention, and
FIGS. 18, 19 and 20 show detector device portions embodying the present invention.
The need for a very sensitive magnetic field detector follows from the smallness of the label beads and that the field anomalies caused thereby in an otherwise more or less uniform externally applied magnetic field are very localized in roughly decaying as 1/r3, where r is the magnitude of the distance from the center of a bead. Because of this highly localized field, only the sensor structure within about one bead diameter sees an appreciable magnetic field effect. Yet, of course, the largest signal possible from a given label bead is desired without suffering nonlinear effects due to bead to bead interactions. The applied field disruption from a label bead that is detected by a sensor is proportional to the magnetization of that bead.
Commercially available paramagnetic beads have either a small, or are entirely devoid of, remnant magnetization (i.e., the magnetization remaining in the bead after an externally applied magnetic field is removed). Consequently, a magnetic detector arrangement requires an additional externally applied magnetic field to magnetize the beads used in any assay. The detector design must be such that detection can take place in an externally applied magnetic field optimal for detection, but not have the detection sensor response saturated, and not mask the field anomaly provided by the presence of a label bead.
In these circumstances, the nature of a label bead anomaly induced in an externally applied field can be approximated by considering a sphere, 10, of paramagnetic material present in a uniform, externally applied, magnetic field of magnitude Happ directed from left to right along the x axis in FIG. 1 parallel to the surface supporting the bead and a magnetic field detector, 11, shown diagrammatically therebelow. (Detector 11 is assumed here to not significantly affect the magnetic fields present.) Using mks units, magnetic induction B (Webers/meter2), magnetic field strength H, and material magnetization M are related as (bold type denoting vector quantities)
where χm is the dimensionless magnetic susceptibility. The entities "magnetizable beads" is defined in terms of the susceptibility χm. While χm can be measured for any material, only some materials have values substantially different from zero (χm of empty space is zero). A paramagnetic material has a single-valued χm just greater than zero, typically ˜0.001, while a ferromagnetic material has a multivalued χm (due to hysteresis) that is much larger than zero (typically ˜1). As will become clear in the following analysis, larger values for χm lead to larger signals at the detector. However, ferromagnetic particles have a tendency to agglomerate because of magnetic attraction to one another (which potentially ruins an assay) and the multivalued nature of χm for such material leads to difficulties in quantification of surface coverage. Consequently, the typical assay employs a paramagnetic material magnetizable bead with as large a χm as possible without causing agglomeration. A spherical bead of a paramagnetic or ferromagnetic material will be uniformly magnetized in a uniform externally applied magnetic field. The external field contribution from the magnetizing of bead 10 will have a dipole distribution based on an effective dipole moment p of
where a is the bead radius, and M (Webers/meter) is the bead magnetization as indicated above.
If the origin is taken at the center of bead 10 in a spherical coordinate system as shown in FIG. 1, this dipole field will have no azimuthal angular dependence and can be represented by just two vector components. These two components of the dipole field at distance r from the center of bead 10 are
where θ is the angle between r and M (which follows the direction of the externally applied field Happ along the x axis). The 1/r3 dependence of these field components can clearly be seen.
The magnetic field contribution alone from bead 10 positioned over magnetic field detector structure 11 in a uniform applied field directed from left to right is roughly depicted in FIG. 2. Similar structures and features in subsequent figures have the same numerical designations as were used in the preceding figures. The total field outside this bead in such an externally applied field will be the sum of the uniform applied field directed from left to right and the field contribution from bead 10 which contribution thus results in an anomaly in the otherwise uniform field present. Note that the field contribution directly under bead 10 in FIG. 2 (field contribution at θ=π/2 in FIG. 1) due to its magnetization directly will oppose the externally applied field thereby decreasing the total field value in this vicinity. The total field Htotal at magnetic field detector structure 11 directly under bead 10 is, as stated, the sum of the externally applied field Happ and the field contribution from bead 10 due to its magnetization, HB, or
since the radial component does not contribute at θ=π/2.
Substituting for Hθ from above yields
A plot of the direction lines of this total field about bead 10 (independent of the azimuthal angle) is shown in FIG. 3 (which assumes that flux arising because of permeable material in a detector structure therebelow is negligible or is confined in a closed flux path therein). If the distance from the bottom surface of bead 10 to the upper surface of magnetic field detector structure 11 is equal to the radius of bead 10 (i.e., at the point having coordinates r=2a, θ=π/2) then
A practical superparamagnetic bead (having a magnetization in a magnetic field much greater than ordinary paramagnetic material) has a value for χm around 0.05, so the total field at magnetic field detector structure 11 would be on the order of
The effect of bead 10 is thus to provide an anomaly in the externally applied field that has the effect of attenuating the total applied field at magnetic field detector structure 11 by about 3%, a change in field value from the value of the externally applied field within the range of detectability of the sensors to be described below. An alternative example provides a fuller representation of this field attenuation situation as shown in FIG. 4 which shows the component parallel to Happ of the field from the particle in the plane of magnetic field detector structure 11, this example based on using values of χm=0.05, a particle radius of 0.5 μm, and a particle-to-GMR separation of 0.1 μm. But this attenuation effect is limited to the region in the immediate vicinity of bead 10. The magnitude of the distortion to the externally applied field because of the presence of bead 10 drops off approximately as 1/r3 in separating from that bead in all directions so that bead 10 must be sufficiently close to magnetic field detector structure 11 if field attenuation in this range is to occur at that structure. Hence, if a single bead is to be detected, it is best to match the size of magnetic field detector structure 11 to the size of bed 10 for maximum resolution.
A suitable arrangement for magnetic field detector structure 11 can be advantageously fabricated using ferromagnetic thin-film materials based on magnetoresistive sensing of magnetic states, or magnetic conditions, thereabout. Such devices may be provided on a surface of a monolithic integrated circuit to provide convenient electrical interconnections between the device and the operating circuitry therefor in the integrated circuit chip.
In the recent past, reducing the thicknesses of the ferromagnetic thin-films and the intermediate layers in extended "sandwich" structures in which the two major surfaces of the intermediate each have thereon an anisotropic ferromagnetic thin-film layer, including those having additional alternating ones of such films and layers, i.e. superlattices, have been shown to lead to a "giant magnetoresistive (GMR) effect" being present. This effect yields a magnetoresistive response which can be in the range of an order of magnitude or more greater than that due to the well-known anisotropic magnetoresistive response.
In the ordinary anisotropic magnetoresistive response, varying differences between the direction of the magnetization vector in the ferromagnetic film and the direction of the sensing current passed through the film lead to varying differences in the effective electrical resistance in the direction of the current. The maximum electrical resistance occurs when the magnetization vector in the film and the current direction are parallel to one another, while the minimum resistance occurs when they are perpendicular to one another. The total electrical resistance in such a magnetoresistive ferromagnetic film can be shown to be given by a constant value, representing the minimum resistance, plus an additional value depending on the angle between the current direction in the film and the magnetization vector therein. This additional resistance follows a square of the cosine of that angle.
As a result, operating external magnetic fields can be used to vary the angle of the magnetization vector in such a film portion with respect to the easy axis of that film portion which comes about because of an anisotropy therein typically resulting from depositing the film in the presence of a fabrication external magnetic field oriented in the plane of the film along the direction desired for the easy axis in the resulting film. During subsequent operation of the device with the resulting film, such operating external magnetic fields can vary the angle to such an extent as to cause switching of the film magnetization vector between two stable states which occur as magnetizations oriented in opposite directions along that easy axis. The state of the magnetization vector in such a film portion can be measured, or sensed, by the change in resistance encountered by current directed through this film portion.
In contrast to this arrangement, the resistance in the plane of a ferromagnetic thin-film is isotropic with respect to the giant magnetoresistive effect, rather than depending on the direction of a sensing current therethrough as for the anisotropic magnetoresistive effect, depends on the cosine of the angle between magnetizations in the two ferromagnetic thin-films on either side of an intermediate layer. In the giant magnetoresistive effect, the electrical resistance through the "sandwich" or superlattice is lower if the magnetizations in the two separated ferromagnetic thin-films are parallel than it is if these magnetizations are antiparallel, i.e. directed in opposing directions. Further, the also present anisotropic magnetoresistive effect in very thin-films is considerably reduced from the bulk values therefor in thicker films due to surface scattering, whereas very thin-films are a fundamental requirement to obtain a significant giant magnetoresistive effect.
In addition, as indicated, the giant magnetoresistive effect can be increased by adding further alternate intermediate and ferromagnetic thin-film layers to extend the "sandwich" or superlattice structure. The giant magnetoresistive effect is sometimes called the "spin valve effect" in view of the explanation that a larger fraction of conduction electrons are allowed to move more freely from one ferromagnetic thin-film layer to another if the magnetizations in these layers are parallel than if they are antiparallel with the result that the magnetization states of the layers act as sort of a valve.
These magnetizations results often come about because of magnetic exchange coupling between the ferromagnetic thin-films separated by the intermediate layers, these intermediate layers typically formed from a nonferromagnetic transition metal. The effect of the exchange coupling between the ferromagnetic thin-film layers is determined to a substantial degree by the thickness of such an intermediate layer therebetween. The effect of the coupling between the separated ferromagnetic thin-film layers has been found to oscillate as a function of this separation thickness between these layers in being ferromagnetic coupling (such that the magnetizations of the separated layers are parallel to one another) and antiferromagnetic coupling (such that the magnetizations of the separated layers are opposed to one another, or antiparallel to one another). Thus, for some separation thicknesses, the layer coupling can be of zero value between extremes of such oscillations.
Exhibiting the giant magnetoresistive effect in a superlattice structure, or in an abbreviated superlattice structure formed by a three layer "sandwich" structure, requires that there be arrangements in connection therewith that permit the establishment alternatively of both parallel and antiparallel orientations of the magnetizations in the alternate ferromagnetic thin-film layers therein. One such arrangement is to have the separated ferromagnetic thin-films in the multilayer structure be antiferromagnetically coupled but to a sufficiently small degree so that the coupling field can be overcome by an external magnetic field.
Another arrangement is to form the ferromagnetic thin-film layers with alternating high and low coercivity materials so that the magnetization of the low coercivity material layers can be reversed without reversing the magnetizations of the others. A further alternative arrangement is to provide "soft" ferromagnetic thin-films and exchange couple every other one of them with an adjacent magnetically hard layer (forming a ferromagnetic thin-film double layer) so that the ferromagnetic double layer will be relatively unaffected by externally applied magnetic fields even though the magnetizations of the other ferromagnetic thin-film layers will be subject to being controlled by such an external field.
One further alternative arrangement, related to the first, is to provide such a multilayer structure that is, however, etched into strips such that demagnetizing effects and currents in such a strip can be used to orient the magnetizations antiparallel, and so that externally applied magnetic fields can orient the magnetizations parallel. Thus, parallel and antiparallel magnetizations can be established in the ferromagnetic thin-films of the structure as desired in a particular use. Such a structure must be fabricated so that any ferromagnetic or anti ferromagnetic coupling between separated ferromagnetic films is not too strong so as to prevent such establishments of film magnetizations using practical interconnection arrangements.
A magnetic field sensor suited for fabrication with dimensions of a few microns or less can be fabricated that provides a suitable response to the presence of very small external magnetic fields and low power dissipation by substituting an electrical insulator for a conductor in the nonmagnetic layer. This sensor can be fabricated using ferromagnetic thin-film materials of similar or different kinds in each of the outer magnetic films provided in a "sandwich" structure on either side of an intermediate nonmagnetic layer which ferromagnetic films may be composite films, but this insulating intermediate nonmagnetic layer permits electrical current to effectively pass therethrough based primarily on a quantum electrodynamic effect "tunneling" current.
This "tunneling" current has a magnitude dependence on the angle between the magnetization vectors in each of the ferromagnetic layers on either side of the intermediate layer due to the transmission barrier provided by this intermediate layer depending on the degree of matching of the spin polarizations of the electrons tunneling therethrough with the spin polarizations of the conduction electrons in the ferromagnetic layers, the latter being set by the layer magnetization directions to provide a "magnetic valve effect". Such an effect results in an effective resistance, or conductance, characterizing this intermediate layer with respect to the "tunneling" current therethrough.
There are many types of magnetoresistive material that can be used. A sandwich type (e.g. 35A NiFeCo/15CoFe/Cu35/15CoFe/35NiFeCo) or a pinned sandwich (e.g. 35A NiFeCo/15CoFe/Cu35/40CoFe/100IrMn, also called a spin valve) are useful arrangements. They have lower saturating fields the structures described for use below, and so are more sensitive, but also more likely to be saturated by any bead magnetizing fields. Anisotropic Magnetoresistive (AMR) films can also be patterned into such devices. The key for all of these will be to get the beads close to the sensitive layer or layers, and to magnetically bias the magnetoresistors such that they give maximum sensitivity to the presence of the beads. Another enhancement to the sensing material is to give it "hard edges" by oxidizing the edges, pinning them with some antiferromagnetic material, or constructing them so that the two magnetic layers contact each other at the edge of the resistor stripe. Resistors prepared this way will have lower hysteresis in the range of magnetic field magnitudes relevant for the assay.
The GMR magnetoresistors typically used here are formed of a succession of thin, alternating magnetic and nonmagnetic metallic layers having aan electrical resistance that is a function of an external magnetic field. This resistance, as stated above, varies with the angle θ between the magnetizations of adjacent magnetic layers with a sin θ dependance, and a typical change from a minimum (i.e., magnetic layers are aligned in parallel) to maximum (i.e., when magnetic layers are aligned antiparallel) resistance is ˜10% of the minimum value. The thin succession of layers is fashioned into sensors as long, thin, rectangular structures but with pointed ends. The observed resistance is then proportional to the length and inversely proportional to the width. A typical sheet resistance is 10 ohms/□. Consequently, such a typical magnetoresistor with a respective width and length of 0.5 and 5.0 microns (10 squares) would have resistance of 100 ohms under parallel magnetic layer magnetizations that increases to 110 ohms (10%) when under antiparallel magnetic layer magnetizations.
The preceding last example, however, assumes instead for convenience that a 1 μm×1 μm GMR detector is positioned directly beneath paramagnetic label bead 10 so that this bead is situated above the upper surface of structure 11 in the z direction. Such a detector would typically have a current therethrough of 5 mA, and a 10Ω to 11Ω resistance change corresponding to Happ ranging from 200 Oe to 0 Oe. This represents the 10% resistance change over 200 Oe as indicated in Figure J. The detector voltage, then, changes at a rate of 25 μV/Oe. The maximum Happ possible without saturating the sensor is 200 Oe. The field attenuation from the bead modeled above is, on average, 0.05 times the Happ. Though the total resistance change will be slightly less than the average field change due to current redistribution within the GMR sensor, assume for now that the net resistance change is exactly proportional to the average field change. Hence, the maximum total signal field is 10 Oe (0.05×200 Oe). The voltage "signal" from the bead is then 250 μV.
The noise of the detector has two main components: thermal noise and current dependent 1/f noise. The thermal (Johnson) noise for a 10Ω resistor is 0.4 nV/{square root over (Hz)}. The detector's intrinsic 1/f noise will typically be two orders of magnitude higher than the thermal noise at 1 Hz, and have a corner frequency at 10 kHz. Assuming a 1 Hz measurement frequency, the total noise will be dominated by the 1/f noise, and be about 40 nV/{square root over (Hz)}. So the signal to noise ratio at 1 Hz with a 1 Hz bandwidth is 250 μV/40 nV=6250:1. While this simple calculation ignores engineering challenges that must be addressed to fully use the available signal, it is clear that detection of a single 1 μm diameter bead with a 1 μm×1 μm GMR detector is not limited by fundamental signal to noise issues.
The relative positional arrangement in FIG. 2 of bead 10 and GMR magnetic field detector structure 11, and the relative orientation of the externally applied magnetic field, can be varied. One variation of the externally applied magnetic field relative orientation is to apply such a field normal to the plane of GMR detector structure 11 as shown in FIG. 5. GMR detector structure 11 is about 1000 times more difficult to magnetize in the direction normal to its major surface than in a direction parallel thereto, and so a much larger magnetizing field can be applied to bead 10 and that structure without saturating the GMR magnetoresistors therein. Here, magnetic field detector structure 11, rather being shown by itself with bead 10 directly thereover, is shown over a space between that structure and a another GMR magnetic field detector structure, 11′.
The use of multiple magnetoresistors in GMR magnetic field detector 11 permits measurement circuit advantages including use of a differential detection, e.g. a bridge circuit detector, arrangement. Although a bead detection site can be provided with only one magnetoresistor as shown in FIG. 2, a bridge circuit having two or more magnetoresistors therein offers several benefits including rejection of common mode noise, and provision of first order temperature compensation. In such a bridge circuit, one or more of several GMR magnetoresistors provided therein are exposed to possible magnetic field anomalies due the possible presence of bead 10 while the remaining magnetoresistors are not so exposed, or are instead exposed to fields in the opposite direction.
One such example is shown in FIGS. 6 and 7. A single bead detection site, 12, formed by the presence of a binding molecule coating, is provided having four GMR magnetoresistors, 13, 14, 15 and 16, as individual sensors electrically connected together the metal interconnections shown in a Wheatstone bridge arrangement between metal interconnections voltage supply terminals, 17 and 18, and located between two flux concentrators, 19 and 20, to be described below. Site 10 is provided so that one pair (active) of magnetoresistors, that is, 13 and 14, are in opposite legs of the bridge circuit and subject to the field anomaly introduced by the presence of bead 10 while the other pair (reference) formed of magnetoresistors 15 and 16 is not so subjected even they are also subjected to the externally applied field. The signal developed across the bridge circuit is provided between two metal interconnections signal terminals, 21 and 22, and provided to the signal inputs of a differential amplifier, 23, providing a corresponding differential output signal at its output, 24.
Keeping these two pairs of magnetoresistors distinguishable as active magnetic field anomaly sensing magnetoresistors and reference magnetic field sensing magnetoresistors during an assay can be accomplished using one or another of several techniques. The simplest way is to provide a covering of a suitable kind such that no bead ever reaches a position sufficiently close to the reference magnetoresistors to magnetically affect them. Alternatively, the detection site can be fabricated, or subsequently modified, so that few or no particles will able to adhere to a surface of, or a surface near, the reference magnetoresistors. In addition, or instead, a passivation layer over the detector surface (the upper or final layer shown over all else) can be kept thick over the reference magnetoresistors as in the layer diagram of FIG. 8 to substantially separate bead 10 therefrom but kept thin over the active magnetoresistors (the upper or final two layers removed over a structure 11 with binding molecule coating 12 there) as shown in the layer diagram of FIG. 9 to allow bead 10 to approach closely.
Flux concentrators 19 and 20 in the form of permeable material masses can be incorporated into a bridge circuit detection arrangement to concentrate externally applied magnetic fields in and about the active magnetoresistors, as shown in FIGS. 6 and 9, or a flux concentrator, 25, can be provided to increase and guide magnetic fields developed in the detector itself through providing current through a conductor coil, 26, formed thereabout as shown in FIG. 10. In each instance, both the active pair and the reference pair of magnetoresistors are shown positioned in the gap between two such concentrating flux concentrators, or in the gap between the two ends of an enhancing and guiding flux concentrator, so that they all will be immersed in substantially the same concentrated externally applied magnetic field.
In such an arrangement, the flux concentrator or concentrators are simply acting as a multiplier of the externally applied magnetic field. The multiplication factor is approximately [concentrator length]/[concentrator separation gap]. Alternatively, the reference magnetoresistors can be positioned underneath the flux concentrators. They will in such a position experience a much smaller net field (they are substantially shielded from the applied field) than the active magnetoresistors positioned in the concentrator gap (the common mode field rejection is then lost) but they will require no space to be provided for them in the gap.
The methods used to fabricated structures like those shown in FIGS. 8 and 9 are based on well known semiconductor device fabrication processes. Two alternative processes will be described, the choice of which depends on whether the resulting devices are to have interconnection metal provided above or below the GMR magnetic field detector structure. If the interconnection metal is to be provided below the GMR magnetic field detector structure, a Si based wafer, 30, which may have monolithic integrated circuitry therein, has a 200 nm layer of substrate Si3N4, 31, supported thereon, on which a 1.5 μm layer of Al is first deposited. This Al layer is patterned using standard photo lithography and a reactive ion etch (RIE) to form what will become the interconnections, 32, for the magnetic field detector, or assay, circuit. A 2.5 μm (must be at least as thick as the previous Al layer) thick layer of Si3N4 is deposited over the patterned Al. Then, the resulting surface is planarized using chemical mechanical polishing (CMP). The Al interconnections are exposed during the CMP, so that the resulting surface of the wafer has both Al and a Si3N4 base, 33, in it. Both materials are smooth. The GMR magnetic field detector structure material is then deposited.
The succession of alternating magnetic and nonmagnetic metallic thin-film layers in the GMR magnetic field detector structure is formed in a vacuum deposition system using rf diode sputtering. The succession thickness is 10 nm to 40 nm, depending upon the particular structure chosen for use. The thicknesses of individual layers within the succession are controlled to tenths of nanometers. The GMR succession is followed by providing thereon a 10 nm CrSi etch stop layer on which is further provided a 40 nm Si3N4 mask layer. The Si3N4 mask layer is patterned using standard photolithography and an RIE etch. The GMR magnetic field detector structure+etch stop succession is then etched through the resulting Si3N4 mask using an ion mill to leave the GMR magnetic field detector structure 11 magnetoresistors, 34. Most or all of the Si3N4 mask is etched away in the ion mill, and at least some or all of the CrSi layer, 35, below this mask remains on these magnetoresistors. At this point, the GMR magnetic field detector structure 11 magnetoresistors and Al interconnections are complete and can be tested.
The GMR magnetoresistors and the Al interconnections are then passivated by providing thereover a thin layer of Si3N4 as a passivation layer, 36. The required thickness of this passivation layer depends upon two things, the step height of the GMR magnetoresistors above the base layer therebelow, and the standoff voltage required between the GMR elements and the bead samples that will be present above the passivation. If some passivation is required and the voltage requirements are minimal, though non-zero (<10 Volts), the passivation layer minimum thickness limitation will be the first requirement for topological coverage of the GMR step edge. A rule of thumb is to use a passivation layer thickness equal to that of the step being covered, although less is possible. A passivation layer thickness of 10 nm is typically sufficient. Such a passivation layer provides a nominal standoff voltage of about 1000 Volts/μm, so a 10 nm passivation will nominally provide 10 V. The resulting detector is shown in FIG. 11 with binding molecule coating 12 thereon over GMR magnetic field detector structure 11 magnetoresistors 34.
If the interconnection metal is to be provided below the GMR magnetic field detector structure, on the other hand, the structures of the layer diagrams in either of FIGS. 8 and 9 can be fabricated. In this situation, the succession of alternating magnetic and nonmagnetic metallic thin-film layers in the GMR magnetic field detector structure is deposited directly upon substrate Si3N4 layer 31 on Si wafer 30 as above. An 10 nm CrSi etch stop layer plus a Si3N4 masking layer of 40 nm thickness is deposited, and then photolithography and RIE are used to pattern the Si3N4 to form an etching mask, followed again by use of an ion mill to etch the GMR magnetic field detector structure+etch stop succession thereby leaving the GMR magnetic field detector structure 11 magnetoresistors. Again, most or all of the Si3N4 mask is gone after this milling, and most or all of CrSi etch stop layer 35 under this mask remains on these magnetoresistors.
Thin Si3N4 passivation layer 36 is then deposited serving here as an inner passivation layer, and passageways, or vias, to the GMR magnetic field detector structure 11 magnetoresistors are etched in inner passivation layer 36 using RIE. A relatively thick Al (˜1 μm) layer is next deposited and patterned using photolithography and RWE, so that interconnections, 37, are made for the GMR magnetic field detector structure 11 magnetoresistors. The Al needs to be thick so that the lead resistance is low compared to the resistance of these magnetoresistors. Exposed surfaces of aluminum interconnections 37 and Si3N4 passivation layer 36 then have deposited thereon a 10 nm aluminum nitride (AIN) layer, 38, for its adhesion properties followed by a 1.5 μm Si3N4 layer, 39, which together form the outer passivation for the device. FIG. 8 shows a layer diagram of the resulting structure at this point of the fabrication process which leaves an outer passivation layer so thick that bead 10 thereon over GMR magnetic field detector structure 11 magnetoresistors would have little magnetic effect on those reference magnetoresistors.
However, to provide active magnetoresistors also, photolithography and RIE are used to remove the Si3N4 portion of the outer passivation layer from selected areas. Such areas include those over bonding pads for external wiring and, of course, those over certain magnetoresistor sites where enhanced sensitivity to magnetic particles is desired. Material milling in an ion mill step is used to remove the exposed AlN layer in these regions in a controlled way, leaving nearly the full thickness of the underlying inner Si3N4 passivation layer, or somewhat less if desired. FIG. 9 shows the layer diagram of the result upon the completion of these steps in the fabrication process if binding molecule coating 12 and flux concentrators 19 and 20 are ignored.
Flux concentrators 19 and 20 can be added at this point for amplifying externally applied fields, or coil 26 and flux concentrator 25 can be added at this point for guiding on-chip fields. A photoresist plating mold is formed, and permalloy is electroplated into the mold to a thickness of about 15 μm to form flux concentrators 19 and 20. FIG. 9 shows the structure resulting to this point in the fabrication process if binding molecule coating 12 is again ignored.
There are many methods to provide binding molecule coating 12, i.e. of preparing the assay probe region, the particulars of which depend upon the intended purpose of the assay. One method to create probes for a DNA hybridization assay is described in the following.
The resulting structure after the flux concentrators are completed is coated with gold using a lift-off mask that leaves gold over large portions of the chip, but such that it does not short different magnetoresistor interconnections together. Then spots of reagents containing thiolated DNA oligomers are dispensed over the intended assay probe region using a Sapphire-tipped Rapidograph pen. In order to keep the non-probe regions inert, the chip surface is also treated with thiolated PEG (O-(2-mercaptoethyl)-o′-methyl-polyethylene glycol 5000. Such a material can be used to complete the device shown in FIG. 9 in providing coating 12 shown there.
The response of a typical GMR magnetic field detector structure magnetoresistor to an external magnetic field is unipolar, linear, and saturates in fields ranging from tens of Oe to a few hundreds of Oe, depending upon the particular magnetic design. A plot of the observed resistance vs. externally applied magnetic field strength for a typical multilayer GMR magnetic field detector structure magnetoresistor is shown in FIG. 12. The presence of a bead 10 is then detected by observing a change in the resistance due to the external field experienced by the magnetoresistor.
Detecting a single magnetizable bead with GMR magnetic field detector structure magnetoresistors at a binding molecule coated assay surface, as essentially set out above, is typically insufficient in view of the overall assay signal-to-noise ratio being proportional to the number of capture sites at the assay surface, i.e. proportional to the square root of the assay surface area over which such sites are provided, assuming a random a real distribution of "noise events". Assay "noise events" include situations like beads sticking where they are not supposed to be sticking in the detection scheme (non assay-specific adhesion, leading to artificially high magnetic signal) and other kinds of particles (other than beads) sticking to detection sites in place of beads (contaminants, for instance, leading to artificially low magnetic signal).
However, individual assay surface sizes on the order of 10 to 1000 μm in diameter often result if formed by techniques that are not lithographically based such as forming the assay surface sites by "spotting" the chip with fluid using a fine plotter-type device or a tiny metal point dipped in an appropriate solution to provide the binding molecule coating. These techniques result in spot sizes much larger than 1 μm. Lithographic techniques, instead, can result in much smaller individual effective detectors over the assay surface.
Thus, assay surfaces that are much larger than a typical bead, say a 50 μm sided square, lead to a desire to measure the surface concentration of beads across the entire surface, or detection site, as accurately as possible. This implies having a detector arrangement with an active region covering as much of the site as possible, and which provides a response to beads captured at the site that is uniform across the site. A GMR magnetic field detector structure magnetoresistor arrangement having multiple effective individual detectors can be provided across such a assay surface, or detection site, by having several individual GMR magnetic field detector structure magnetoresistors electrically connected together in series.
FIG. 13 shows a top view of such a detector arrangement in a portion of a device formed on an integrated circuit under a square binding molecule coating forming detection site 12 in which the individual GMR magnetic field detector structure magnetoresistors are each approximately 4 μm wide, separated by 2 μm, and connected together using Al metal interconnections 37 formed over the top of the series connected magnetoresistors. Passivation layers and any flux concentrators used are omitted from this view for clarity. These magnetoresistors are individual sensors like the magnetoresistors in FIG. 6 and so designated 13, 13′, 13″, 13′″, 13″″, 13 v, 13 vi and 13 vii in representing an active group of magnetoresistors. The "active region", or detection site 12, is a square 50 μm on a side that is effectively defined by the existence of the binding molecule coating "assay surface" and possibly other construction features such as thinned sensor passivation, etc.
In situations where a full Wheatstone bridge circuit is desired to be used, the same assay surface can be monitored by two series connected, interleaved GMR magnetic field detector structure magnetoresistor groups connected as shown in FIG. 14 for again a portion of a detector device formed on an integrated circuit with some layers omitted for clarity. These groups are again taken as like the magnetoresistors in FIG. 6 and so designated 13, 13′, 13″ and 13′″ for one group of active resistors, and designated 14, 14′, 14″ and 14′″ for the other group of active resistors. The gap between two adjacent magnetoresistors is ideally as small as possible to maximize surface coverage, but is limited in coverage by practical lithographical spacing considerations. The width of each of the magnetoresistors can vary over a wide range, from the narrowest that can be fabricated (<0.5 μm) in the best resolution fabrication process to as wide as the entire assay site if only one or two magnetoresistors are to be used. The length-to-width ratio of each of the magnetoresistors is to be such that the resistance total of the groups satisfies detection circuit criteria. For example, some preamplifiers operate best with a source impedance of about 1 kΩ which requires 100 squares of 10Ω/square material. The resistor in FIG. 13 has 8 legs, each 4 μm×50 μm=12.5 squares=125Ω for a total of 1 kΩ.
The width of an individual magnetoresistor is also important because the most sensitive region of such a magnetoresistor is in the interior thereof because the edges thereof are magnetically relatively stiff in resistor rotation of the magnetization in those regions. Wider resistors, in so having a proportionally larger sensitive region, will thus be more sensitive. On the other hand, wider resistors require more current to generate the same voltage signal because of reduced resistance. Too much current can generate excess heat which may disturb or destroy the coating forming the assay surface or affect the test in other ways.
The system sensitivity to a single bead is enhanced by using multiple GMR magnetic field detector structure magnetoresistors with respect to such a bead so that more than one of those magnetoresistors is affected by the magnetic field anomaly introduced by the presence of a bead. Thus, rather than having the bead come to a position directly above a magnetoresistor, the bead would instead be directed to a position between two adjacent magnetoresistors, or even in the area between four such magnetoresistors. A channel can be provided between each member of a pair of magnetoresistors, or a hole could be provided in the area between four magnetoresistors, in which the beads would be more likely to be captured, and in which the binding molecule coating forming the assay surface would be placed. Such an arrangement is shown in FIG. 15 in which a bridge circuit is shown formed in a portion of the detector arrangement provided on a monolithic integrated circuit having detection site 12 located between active magnetoresistors 13 and 14 where each will experience the magnetic field anomaly introduced by the presence of a bead 10 bound to site 12 while more remotely located reference magnetoresistors 15 and 16 will not.
The depth of these channels or holes, 40, should be such that the center of the bead is level with the magnetoresistors in the vertical direction as is shown in FIG. 16 which is a portion of a layer diagram of the device portion shown in FIG. 15 and an enhancement of the structure shown in FIG. 9. This arrangement is advantageous when using an externally applied excitation magnetic field that is directed parallel to the major surfaces of the magnetoresistors as in FIG. 15 which could be alternating direction fields. The response magnetic field from the bead would be similarly directed, and the resulting poles of the bead would be very close to the magnetoresistor edge for properly chosen magnetoresistor dimensions. The alternative situation for the arrangement of FIG. 15 is to rely just on the binding molecule coating to keep a bead 10 between magnetoresistors 13 and 14 as shown in FIG. 17.
Word lines, or structures like them, can be used to generate such externally applied fields on-chip that either supplement or eliminate off-chip magnetic field generating. Permeable mass flux keepers can be used to direct the flux from the lines and from the beads. Use of a buried word line would allow the beads to be close to the magnetoresistors as does the use of buried connectors as shown in FIG. 11. Alternatively, the externally applied excitation magnetic fields could be directed perpendicularly to the major surfaces of the magnetoresistors but then off-chip magnetic field generating is likely to be needed.
The FIG. 17 arrangement relying just on the binding molecule coating to keep a bead 10 in place is ideal if patterning the binding molecule coating is performed to provide portions thereof just where the magnetizable beads are desired to be attached. This way, the beads would stick only where they impart the largest field to the magnetoresistors. The form of the pattern would depend on what sensing mode one was being used. If the externally applied excitation magnetic field orientation was perpendicular to major surfaces of the magnetoresistors, the beads should come to be positioned next to or on top of the magnetoresistors as shown in FIGS. 18 and 19 which alternatively show the magnetoresistors interconnections above and below the magnetoresistors, respectively. Since only one magnetoresistor 13 is actively affected by bead 10 here, the other magnetoresistor in the bridge circuit previously described as also being active in other arrangements has been redesignated 14′ here. If the excitation orientation is parallel, the beads should come to be positioned on the magnetoresistors or between two magnetoresistors as in FIGS. 15, 16 and 17. Of course, the binding molecule coating material to which the beads come to stick to in a position must thin with respect to the thickness of detection devices layers (<1 μm). If the coating is instead tens of μm thick, then any magnetoresistor arrangement will be insensitive.
The magnetic field anomaly arising from the presence of a micron sized magnetizable bead is, in actuality, often very non-uniform and can be best detected in a differential mode using a gradiometer magnetic field measurement arrangement. In most situations, this means a bridge circuit configuration where one or two magnetoresistors of a four magnetoresistor bridge circuit experience the effects of the presence of a bead while the other two are not. That is, the "active" magnetoresistors are under the influence of the presence of a bead and the "reference" magnetoresistors are not.
If embedded externally applied magnetic field excitation coil straps and thick permeable masses as flux "pipes" are used on-chip to generate such externally applied magnetic fields locally around magnetoresistors, the presence of beads near the straps or resistors will change the local field distribution. Such bead presence will also change the field distribution in the gap between two flux concentrators. If a magnetoresistor is in the gap between two flux concentrators, the magnetic field experienced by them in the gap for the occurrence of an externally applied field will be reduced by the presence of a bead in the gap because they concentrate flux therethrough from the gap region and the magnetoresistors. A bridge sensor can be made to use this property by putting two magnetoresistors in a gap between flux concentrators where beads are allowed, or even promoted, to stick while putting two identical magnetoresistors resistors in an otherwise identical gap between flux concentrators where beads are not allowed or promoted to stick. The externally applied magnetic field could be generated by on-chip current conductors located under the flux concentrators.
Beads near current conductors will redistribute magnetic flux generated by the current as well. If the beads are on the same side of the conductors as a magnetoresistor, the current generated magnetic field at the magnetoresistor due to current in the conductor will be reduced. If the beads are on the opposite side of the conductor from the magnetoresistor, the current generated magnetic field will be increased. In the former situation, the beads form a higher magnetic permeability path and concentrate flux away from the magnetoresistor. In the latter case, the lower permeability of the beads permits a larger amount of flux to go around the conductor for a given amount of current therethrough.
If a magnetoresistor is fabricated with the sensitive axis perpendicular to its direction of longest extent, with a buried, parallel current conductor provided around it at a fixed separation, the field along the sensitive axis would be zero at the magnetoresistor. If a bead came to be positioned above the conductor on one side of the magnetoresistor, the field would become unbalanced at the GMR resistor and a net field would be experienced to provide the basis for a four-magnetoresistor bridge circuit to generate an offset dependent output signal.
Typical magnetizable beads for assays require magnetic fields of several hundred to over a thousand Oe for saturation. Consequently, there is a mismatch between the field ranges of GMR magnetic field detector structure magnetoresistor and the fields required to significantly magnetize the beads. Because the saturation field for the beads is so large compared to the magnetoresistors, an arrangement to provide different flux densities for an externally applied excitation magnetic field would help. This can be done by making a permeable mass based flux loop on the detector surface with two types of gaps therein as shown in the detector arrangement portion shown in FIG. 20 with the permeable masses designated 19′ and 20′. One gap is for beads in binding molecule coating region 12, and the other gap is for the active magnetoresistors. The reference magnetoresistors are positioned under the flux loop mass (shown schematically), or under other permeable mass shields. Both gaps have the same length along sensitive axes of the magnetoresistors (though this is not necessary). The gap for beads would be much narrower than the gap for the magnetoresistors. So while the same flux would pass across both gaps, the flux density would be much lower at the active magnetoresistor gap than at the bead gap. The flux loop permeable mass would ideally has coil 26 wound therearound for current to generate the externally applied field. Alternatively, that field could be generated by an underlying planar coil.
Although the present invention has been described with reference to preferred embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.
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Diego, Kamper, and Mapp shreddin at ski rixen! the weather wasn't holding up so had to cut the shoot a little short, full feature coming soon!
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Tests are small, automated Ruby programs that automatically test different parts of your applications. After writing some tests, you can run them using the "rake" command line application. Treehouse Ruby teacher Jason shows you how to run tests in this Quick Tip.
Running Tests in Ruby on Rails – Treehouse Quick Tip
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For nearly three seasons, Basketball Wives has explored the drama between a core group of women who at one point or another have all had it out with each other, with varying degrees of violence, anger, and…creative language. And of course when women behave badly, they come under fire for it, and the women on this show certainly receive their fair share of criticism. Shaunie O'Neal, who not only stars on the show but executive produces, is fully aware of the negativity directed toward the show, and in a commentary she wrote for CNN.com, O'Neal acknowledges and defends the women of Basketball Wives.
We've pulled some highlights from her piece which address the biggest issues from the show, feel free to read the entire thing over on CNN, and weigh in on Shaunie's defense in the comments. Shaunie writes:
I have gotten both good and bad responses from viewers about "Basketball Wives," and I certainly understand the opinion that the shows portrayal of black women is beginning to look somewhat negative.
As you see on the show, I'm not a big supporter of the bickering, drink throwing and fighting, but when you put a group of strong, independent and vocal women who are going through or just came out of a bad relationship together, there's bound to be a little drama…
The problem for me is when black women are portrayed as only being that way and labeled different than their non-black counterparts for the same type of behavior. That's when it becomes negative and damaging to our image.
I'm not saying we have to create shows that only paint a pretty picture about who we are, but there should be a balance and most of all some integrity to the shows we create.
That's why I wanted to do "Basketball Wives." I wanted to show what life is really like when you are with a professional athlete — and that sometimes all that glitters isn't gold…
That's the heart of "Basketball Wives," and I believe that if you look closely and beyond the arguing and the fighting, you'll see a group of women trying to get their lives back on track and figure out who they really are.
Commentary: Negative portrayals of black women on reality TV [CNN]
[Photo: Getty Images]


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in this issue
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EnviroTech :: Regulatory
Paint Companies Denied New Trial; File Appeal
10:15 AM MDT | July 27, 2007 | Kara Sissell
Former lead-based paint manufacturers have filed an appeal to the Rhode Island Supreme Court (Providence) asking it to overturn a lower court verdict in a lead-based paint public nuisance suit. A jury returned a guilty verdict last year against Sherwin-Williams, NL Industries, and Millennium Holdings, all of which were sued by the state attorney general to recover the cleanup cost of lead-based paint in public buildings and homes. The Superior Court judge ruled last month on financial damages stemming from the jury verdict, ordering the companies to remove the...
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MILWAUKEE (WITI) — It's not exactly the kind of weather that's helpful for teaching.
"It's kind of ironic that when the school year comes around all of a sudden Mother Nature plays a cruel joke on us," says Franklin Pierce Elementary Principal Keith Carrington.
But Franklin Pierce Elementary is doing what it can to keep kids comfortable.
Teachers are making sure students are drinking plenty of water by giving them breaks every 15 to 20 minutes to go to the bubbler.
"I think it's very uncomfortable so that's why I carry a full bottle of water every single day to stay hydrated," says 5th grader Abril Jimenez.
Water stations have also been set up around the building, and school officials are watching the weather closely around recess time.
"If recess is happening especially at the hottest period of the day we will limit that or keep it indoors altogether," says Milwaukee Public Schools Spokesperson Tony Tagliavia.
All Milwaukee Public Schools are following this same protocol.
Since a limited number of MPS schools have air conditioning, some teachers are moving kids out of the classroom.
"Utilizing cooler parts of the school, if there is air-conditioned parts of the building or basement portions of the building, making sure classrooms can go down there to rotate through to keep cool," says Tagliavia.
Franklin Pierce Elementary is one of those schools without AC, but they're doing what they can in the given circumstances.
"I suggested turn the lights off, keeping the shades down so that the sunshine doesn't come in as bright and there are fans in the majority of the rooms," says Carrington.
This problem won't last long, because in a matter of days the fall-like weather will arrive.


text:
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The handsome male model Johnny is looking for a stylist for him. Have a test of your skill here in the game Johnny Depp Dressup. Select the clothes, shoes, glasses, shirt for him. Design the hire style for him. Click and drag the articles on him. Drag the items away which are not suitable for him. You can print your perfect work after your designing.
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Animal Cruelty : A Multidisciplinary Approach to Understandingby Brewster, Mary P.; Reyes, Cassandra L.
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Renting is easy, fast, and cheap! Renting from eCampus.com can save you hundreds of dollars compared to the cost of new or used books each semester. At the end of the semester, simply ship the book back to us with a free UPS shipping label! No need to worry about selling it back.
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Returning books is as easy as possible. As your rental due date approaches, we will email you several courtesy reminders. When you are ready to return, you can print a free UPS shipping label from our website at any time. Then, just return the book to your UPS driver or any staffed UPS location. You can even use the same box we shipped it in!
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This is the edition with a publication date of 5/7/2013.
What is included with this book?
- The New copy of this book will include any supplemental materials advertised. Please check the title of the book to determine if it should include any CDs, lab manuals, study guides, etc.
- The Rental copy of this book is not guaranteed to include any supplemental materials. You may receive a brand new copy, but typically, only the book itself.
Animal Cruelty is an edited volume that addresses all critical aspects of animal cruelty including: its history and prevalence; related legislation; special types of cruelty (hoarding, poaching, blood sports, etc.); its link to other types of violence and crime; theories used to explain animal cruelty; the role of the media; and emerging issues related to animal cruelty. The text is suitable for undergraduate and graduate classes in criminal justice, criminology, psychology, law, sociology, animal studies, and other disciplines, and is especially well-suited for use in classes on such topics as animal cruelty, animal welfare, deviant behavior, animal law, violent crime, veterinary studies, abnormal psychology, and animal husbandry.


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News Section: Schools and Education
School Board Candidate Rodney Jones Says Culture Change Pivotal for District
|Image via candidate's Facebook page
BRADENTON – Rodney Jones describes his candidacy for the District 2 seat of the Manatee School Board as "somewhat of a natural progression." A Manatee County native whose mother was a career educator, Jones talked about his experience with budgets and community involvement in an interview with the Times.
"I felt like the board could use some fresh blood," he says. If elected, Jones would be replacing Barbara Harvey, a 16-year member of the school board, who has yet to announce whether she will run again.
Jones was involved in mentoring at various programs for troubled youth for more than 20 years, including working as a clinical manager at Manatee Glens, and at residential delinquency programs in Arcadia and in Hardee County. Recently, he was employed at SCF as a project manager for a short-term grant deal. He is currently doing substitute teaching in the district, he says, "to see what teachers experience on a day to day basis."
Along with having experience as a grant writer, Jones is also on the district's Citizens Budget Advisory Committee. "I've managed multi-million dollar budgets, but I also understand the mission of the district is to educate children." He says that while kids are "still making significant gains," recent budget issues and news about scandals within the district have overshadowed those improvements.
Jones called the district one with low morale, plagued by widespread concerns over job security due to financial issues, and talked about a cultural change being necessary to raise morale.
The solution, he says, begins with the board, whose members Jones feels often appear too contentious and divided. "It all starts at the top," he explained. "They need to present themselves in a more cohesive way to the community ... because if they present themselves in a chaotic fashion, where we're not getting along, that trickles all the way down."
Major cultural change, he says, may not happen for some time in a district that is the largest business in the county, with more than 6,000 employees.
"This is not a small ship; you're probably talking about 7-10 years for a complete turnaround," he adds.
Absent Harvey, Jones will face Manatee High School teacher Charlie Kennedy for the seat in the August primary.
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text: Warning: Declaration of vB_ProfileBlock_Blog::block_is_enabled() should be compatible with that of vB_ProfileBlock::block_is_enabled() in ..../includes/class_profileblock_blog.php on line 436 View Profile: thanatos - KnoxBlab Register Help Remember Me? What's New? Articles Forum New Posts FAQ Calendar Community Groups Albums Member List Forum Actions Mark Forums Read Quick Links Today's Posts View Site Leaders Blogs Advanced Search Member List thanatos If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. thanatos Member Find latest posts Find latest started threads View Articles View Blog Entries Mini Statistics Join Date 03-24-2009 Last Activity 04-24-2013 05:54 PM Blog Entries 0 Recent Visitors The last 8 visitor(s) to this page were: crooked-finger, Johnny Ringo, pages, PrinceWince, Rocky Hillian, Sappho, Shinola, thedisobedients This page has had 706 visits Tab Content thanatos's Activity Visitor Messages About Me Tab Content All thanatos Friends Photos New Activity () Please reload this page to view the 200+ new activity items that have been created. Older Activity More Activity No More Results No Recent Activity 1 Visitor Messages crooked-finger - 01-06-2011 09:42 AM View Conversation Are you on zh as thanatos too? sorry, pms don't work for me. Showing Visitor Messages 1 to 1 of 1 About thanatos Basic Information Signature Currently building my christian mingle profile. Check back for updates. Statistics Total Posts Total Posts 287 Posts Per Day 0.12 Visitor Messages Total Messages 1 Most Recent Message 01-06-2011 09:42 AM Visitor Messages for thanatos General Information Last Activity 04-24-2013 05:54 PM Join Date 03-24-2009 Referrals 0 -- vB4 Default Style -- Default Mobile Style Contact Us Archive Top All times are GMT -4. The time now is 09:18 AM. Powered by vBulletin® Version 4.2.2 Copyright © 2015 vBulletin Solutions, Inc. All rights reserved.


text:
By Master Sgt. Bob Haskell, USASpecial to American Forces Press Service
KEYSTONE, Colo., May 28, 2004 Qatar is not as hellishly hot in November and December as it is in July and August. But the 80- to 90-degree days and the 40- degree nights in that small desert land between Saudi Arabia and the Persian Gulf can raise havoc with people who are not physically fit.
That is a lesson that some members of the New York Air National Guard out of upstate Syracuse learned for themselves in Qatar during the last two months of 2003, said Col. (Dr.) Reid Muller, commander of the 174th Fighter Wing's medical group. He is also a practicing cardiologist.
"There was a period of adjustment, and it would have been a little easier for some of the people if they had been paying better attention to their physical fitness," recalled Muller, who appears to be superbly conditioned himself and staunchly advocates the Air National Guard's new fitness program.
Muller helped prepare the program that Col. Sylvia Nye is administering for this country's 108,000 Air Guard members. Nye is a nurse and fitness advocate who maintains that good physical fitness enhances people's overall health and quality of life.
That is the long-range benefit of the program that the Air Guard started last year. It focuses on five areas: body composition, cardio-respiratory, flexibility, muscular strength, and endurance, explained Nye in mid-May during the Air Guard's Readiness Frontiers Medical Conference high in the Colorado Rockies.
"This isn't just about taking an annual physical fitness test," Nye said. "This is about enhancing our Guard members' lifestyles. We can help people who do not do well in the tests improve their diets and exercise programs so they will feel better about themselves and perform better in their everyday activities, thus improving their test scores."
The more pressing objective, however, is to improve the physical fitness of Air Guard personnel who are being deployed, sometimes on short notice, to harsh terrain during the global war against terrorism.
"Physical fitness is a command program, because commanders need to know the fitness of their people as well as their airplanes and other equipment," Nye said.
"We have to become a more fit force. We are deploying to rugged and remote areas," said Col. (Dr.) Randall Falk, the National Guard Bureau's air surgeon, who is Nye's boss. "We're serving under austere conditions. We're not going just to Ramstein Air Base in Germany or to Andrews Air Force Base in Maryland, (which) have all of the creature comforts, advanced medical support and neighborhood pharmacies. A fit force suffers fewer occupational injuries and illnesses."
That message has come from the top. Air Force chief of staff Gen. John P. Jumper is emphasizing improved fitness for all Air Force personnel in the active and reserve components, Nye explained, so they are ready to deploy.
That has led to a standard physical fitness test for people in the active, Guard and Reserve forces, Nye added, as well as the idea that everyone develop a workout schedule for at least three times each week.
The test includes running or a three-minute step test, abdominal circumference measurements, push-ups, sit-ups and stretching, Nye explained. The Air Guard goes a step further, she said. It's called the Fitnessage Program. It is a way of determining how each member's fitness scores compare with their chronological ages.
The average age for the 67,000 people tested last year was 36, Nye said. The average fitness age was also 36, she added. That is a pretty good sign that, overall, Air Guard people are in pretty good physical condition, she said. But fitness is a personal matter, and some people are in considerably better shape than others, she added.
Those who are not physically fit may find the adjustment considerably harder in hot or cold or high-altitude environments than those who are, Nye and Muller indicated.
"If you want to thrive and make your life a lot more enjoyable, it's better to be in shape and stay in shape," Muller said. "There is no excuse for not being fit. If you are not in shape, you will be mission-ineffective."
(Army Master Sgt. Bob Haskell is assigned to the National Guard Bureau, Arlington, Va.)
Related Sites:National Guard BureauNew York Air National Guard174th Fighter Wing


text:
With Tibia MULTI-ip changer you can play on OPEN TIBIA SERVERS. IP-Changer can connect your muliti clients with OTS in this same time. You need only one version of program to connect with OTS for diffrent protocol. The easiest interface in this type of program.
In this little free game, you need to help him catch as many falling Duff barrels as he can and carry them to his car's trunk. But don't be deceived, the task is not as easy as it seems since Homer only can carry one barrel at a time, and needs to avoid the flaming barrels. An entertaining game, for sure.
The Geospatial Toolkit (GsT) is an NREL-developed map-based software application that integrates resource data and other geographic information systems . The available resources for different countries allows you to see, calculate and manage the informations you got.
In this game, you are Moe, the owner of the bar which Homer Simpson frequents for a drink. Moe must answer 15 questions to be named "#1 fanboy". Despite the name of the game, the questions refer not only to The Simpsons and Futurama shows, but also to other TV programs such as Family Guy and South Park.
Simpson The Beer Junkie free online arcade game will make you laugh like no game before.
We all know Duffs is the beer Homer loves the most. Now it is up to you to help Homer catch beer barrels falling from the sky.
When you catch one you have to take it to the trunk of Marge's car to catch another one. But not all beer is good for Homer.
Tibia is a pretty old game, launched about 15 years ago by CipSoft GmbH. Unfortunately, especially after prolonged playing, some actions can become quite boring and repetitive. This "bot" have been created to help with this repetitive actions, and therefore, to make playing Tibia a more pleasant experience.
Homer's playing style and featured analysis are unique in the chessworld. Homer offers a completely new way improving your personal playing strength and style in chess. Homer's "Style-System" allows you playing or analyzing games. Try Homer and improve your chess playing strength and style today !
Tibia Map Viewer is a useful freeware and Open Source application that allows you to view maps generated by Tibia game client and create or edit map symbols.
You can view the entire Tibia map you have explored, both upper and lower levels of the map, with zoom ratio from 25 to 400 percents.
Attribute Changer is a powerful Windows Explorer add-on, available at your fingertips whenever you right-click on files, folders or drives in Windows Explorer … for free.Attribute Changer is a powerful Windows Explorer add-on, available at your fingertips whenever you right-click on files, folders or drives in Windows Explorer … for free.
Windows 7 Logon Background Changer is a tiny program, based on WPF, that could be used very easily by the users that have a decent GPU for 3D animations.
Windows 7 Logon Background Changer creates some JPEG files based on the image that is desired to set as wallpaper for the Windows 7 login screen.
This tool includes various effects developing different tones of the voice. It enables you to record the voice, analyze it and add different effects to the recording.
This program serves such purposes as voice messages, presentations, online greeting and animated cards, voiceover, making audio- and video clips etc.
Tibia is an entertaining multiplayer online role-playing game. The game faces you with the challenge of developing the skills of your selected characters, exploring a large variety of areas and dangerous dungeons and interacting with other players in a social and diplomatic level.
This software allows you to change (spoof) Media Access Control (MAC) Address of your Network Interface Card (NIC) or Wireless Network Card (WiFi).This software allows you to change IP Address, Gateway, DNS Servers, IPv6 support, enable/disable DHCP in one click, network configuration presets and many more features.
AV Voice Changer Software is a neat and easy-to-use application that lets you change your voice. Adding effects in order to enhance your voice or changing it in real-time in order to conceal your true identity is also possible. It includes handy additional tools and features such as a recorder, a voice comparator or an audio player.
Voxal Plus Edition is a state of the art voice changer software to edit and add effects to voice recordings. You can also change your voice in real time as you talk into the microphone on your Windows PC.
Extension Changer is a tool which I found to be similar to MAC OS X applications in many ways. And it does exactly what its name says: changes file extensions. I've been using computers since I was a child, but I was never able to understand the purpose of this kind of applications. My logic tells me that it's easier to manually change the extension of a file than to install a tool for this.
Active Password Changer is a powerful solution designed for resetting local administrator and user passwords in case it is forgotten or lost. With this incredible program, you will never have to re-install and re-configure the operating system when you lose or forget the password.
AV Voice Changer Software GOLD will be the tool-of-choice for any media lovers who want to be on the cutting edge of audio technology, able to modify the latest songs available online, or who want to just have a fun time in cyberspace. Media lovers can use the software to create exciting conversation environments for chat zone fun, fun phone conversations, or while playing games online.


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In a decision that probably won't get much press, the California Fish and Game Commission at its meeting in San Diego yesterday rejected a petition by a small group of fishermen to increase the catch limits for market squid. The Commission followed that decision with another asking conservation stakeholders to develop a draft of a new policy for managing forage species, such as squid. Both of these decisions could have long-term ramifications for birds and other wildlife off our shores.
Squid are the keystone prey item for dozens of visiting and breeding seabirds off of California including Albatrosses, Common Murre, Ashy Storm-Petrel and Sooty Shearwater. Squid is also now the most lucrative commercial fishery in California.
The decision on the catch limits came after Audubon, Oceana, the Natural Resources Defense Council and Ocean Conservancy argued against the increase. This coalition has contended that the current catch limit is already too high, and that these food resources are necessary to support birds and other marine wildlife. The fishermen made the request to take advantage of a boom in squid off our shores, while opponents argued that taking more squid would not only undermine wildlife populations, but also destabilize the always delicate squid fishery. Leaders in the squid industry concurred that it would be unwise to change the quota without more information on squid population dynamics.
Audubon and Oceana contend that the root of the problem is that California lacks an overall policy for forage species that recognizes their unique role in the ecosystem. The state's fisheries management plan for squid fails to account for the needs of seabirds and other marine wildlife. Both organizations are continuing to push Assembly Bill 1299, which would compel the state to take into account the larger ecosystem needs when setting limits on forage species catch.
The lack of a forage species policy came up again during the discussion of the squid catch. Several Commissioners acknowledged that the state's lack of a policy for forage species may be undermining wildlife and our economy, and made a motion to invite stakeholders to draft a forage species plan for their formal review. Audubon will be at the forefront of this effort.


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WORCESTER, Mass. – Holy Cross head softball coach Brian Claypool has announced a change in this weekend's winter clinic schedule. The Sunday, Feb. 24, session, open to ages 8-17, has been moved up to Saturday, Feb. 23, due to the forecasted winter storm. The two sessions originally scheduled for Saturday will still take place as planned.
Claypool and the rest of the softball staff announced on Jan. 31 that the team will hold three winter clinic sessions for student-athletes ranging from ages 8-17. The first session will be held from 10:00 a.m. to 12:30 p.m. for ages 8-12 and the second session will run from 1:00 p.m. to 4:00 p.m. for ages 13-17. The third session will be open to ages 8-17, and will now also run on Saturday from 10:00 a.m. to 12:00 p.m. All three sessions will take place at the Holy Cross Field House in Worcester, Mass.
Holy Cross staff and members of the softball team will be teaching and engaging clinic participants during all three sessions. The 8-12 age group will focus on throwing and fielding fundamentals and the foundations of hitting while the 13-17 age group will focus on throwing, infield and outfield defensive work, base running and hitting mechanics. The rescheduled 8-17 age group session will focus specifically on pitching.
Session prices range from $60-$75 and there are $20-$25 discounts for any immediate family members also attending the clinics. Team discounts are also available.
If interested, please call the Holy Cross softball office at 508-793-3627 to reserve your spot. Then, fill out the registration form and bring the application plus payment to the clinic on Feb. 23. To inquire about team discounts, contact email@example.com or call the softball office.


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My name is Cheryl Thornton Hand. Although I have been teaching high school students for 24 years, this is my ninth year at HHS.
I am a Summa Cum Laude graduate of Auburn University with a B.S.E. in mathematics and a M.Ed. in mathematics. I have an Ed.S. in mathematics from AUM.
I have one son, Jackson, who is in the seventh grade at Holtville Middle School. I enjoy reading, running, traveling, and Auburn football!
Copyright © 2015 Holtville High School


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Beginning this semester, McGraw-Hill Higher Education will make its industry-leading personal digital tutor – McGraw-Hill LearnSmart – available for students to purchase directly. Traditionally, McGraw-Hill has marketed LearnSmart, which is available in almost every subject area, to universities and professors for class-wide adoption, which it will continue to do. But now, students can access LearnSmart on their own – a move the company made because of the solution's growing popularity and proven effectiveness among students.
Students using McGraw-Hill LearnSmart have been proven to move up a full letter grade by studying smarter, not longer. With LearnSmart, students use their out-of-class study time to answer questions that are related to what they're learning in their course. The fully digital system acts like a personal tutor, continuously assessing students' knowledge and skills and providing personalized content and recommendations that help them master basic course concepts and retain their knowledge over time. Because LearnSmart is conveniently accessible online and via mobile apps, the technology and devices that students use every day will power a personalized, study-on-the-go experience that will give them the information and focus they need to ensure success in their courses.


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- 114Promote
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Untitled 10by Alex G Griffiths
Collect your choice of gallery quality Giclée, or fine art prints custom trimmed by hand in a variety of sizes with a white border for framing.
Well done!
wow so delicate :D
Love your style! This is really cool
Love this!
wonderful style!
Thanks for all your comments guys :)
I love your style.
superb drawing!
sweet, love his umbrella!
Thanks a lot Cynthia, Eric and Twiggs!
love this one!!!!
Me too, I like this one very much (::
What a cute kiwi(?) :D
Im not sure to be honest haha... Let's say kiwi :)
this bird makes me happy :)
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New player safety rules, more research on better protection and better teaching techniques are just a few of the ways the NFL has been trying to make football safer. But how effective have these changes been? USA Today spoke with multiple sources to find out to see if what the NFL is doing to try to make the game safer is really working. Read More
Home / Breaking News / NFL's safety changes slow to take hold this season
Tagged with: athlete concussion Football football player safety football safety injury injury prevention NFL NFL player safety player safety player safety rules reduce injuries reduce injury safety education sport Sport Safety Sports Safety USA today


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Actually, one of my favorite "there are wizards among us" stories is entitled "El Regalo" (The Gift) by Peter S Beagle (of The Last Unicorn fame.) Part of his anthology The Line Between, Beagle chronicles the misadventures of a 15 year old Korean American girl named Angie and her 8½ year old brother named Marvyn, both of whom come to discover that they have magical powers. In this tantalizing tidbit that is just calling to be expanded to a full length novel, they find themselves pitted against an ancient, malevolent sorceror only known as El Viejo, The Old Man.
The multicultural environs necessarily places this novella in a major metropolitan area. Given my Southern California-centrism, I immediately imagine that this is L.A. (Beagle did write a novel entitled Unicorn Sonata that was set in L.A.) But I suppose this could just as easily be NYC, particularly since Beagle grew up there.
Which leads to why, of all the fantasy series that I've read, The Earthsea Cycle exercises such a strong hold on my imagination.
Never mind the wonderful elucidation of the system of Magic, the interweavings of Taoist philosophy, and the beauty and the lyricism of Le Guin's writing. True, these alone make the series worth reading. But as a person-of-color who aspires to be a writer of speculative fiction, the fact that Ged is a brown guy is awesome.
Pam Noles' essay on how groundbreaking it was to have a non-white major character pretty much encompasses anything I have to say about the subject, and is far more articulate than anything I could write. But suffice it to say that I was eminently saddened by the Sci-Fi Channel's wanton rape of Le Guin's material, of which UKL herself has much to write about: (1) A Whitewashed Earthsea: how the Sci Fi Channel wrecked my books (2) Frankenstein's Earthsea.
But Earthsea resonates with me and my cultural heritage far more than just due to the coincident skin color. I ought to write UKL some day to ask her if certain concepts were deliberate. Like Ged himself, my parents come from an archipelago. My distant ancestors were all seafarers, some of whom braved the open seas, reaching as far as Madagascar to the west and Easter Island to the east, and some even theorize that they might have actually made it to the South American mainland. And in the beginning of certain Filipino creation stories, just like the creation myth of Earthsea, there was only sea and sky.
The Old Powers recall the indigenous animistic beliefs of Southeast Asia. And even the magic system, where to name something is to bind it, resonates.
(Not that this has anything to do with it, but the concept of the Verdunan, the Division, is key to the final book in the cycle. For some reason, I automatically think of the Ati-Atihan, which is a festival on the isle of Aklan which supposedly commemorates the arrival of the Borneans and their agreement to share the land with the indigenous Ati. And these are probably just false cognates, but what if Ati is related to the word "hati", which means "half" in some Austronesian languages. Given the typically diminuitive stature of the Ati, does this connote "halfling"? OK, I've probably read way too much J.R.R. Tolkien. But getting back to the Verdunan, what if the Ati-Atihan is actually hati-hati'an, meaning "division", which makes sense if the festival commemorates the partition of the island between the Ati and the Borneans. Anyway.)
In summary, The Earthsea Cycle inspired me to find my own authentic voice with regards to speculative fiction, to leverage my unique cultural background in order to build worlds that have not yet been described. I have yet to actually take pen to paper. And while I lament that there have yet to be any Filipino Americans to brave the genre of science-fiction and fantasy, I know that there are writers out there, some of whom are writing such stories. And I can't really say much unless I'm going to put in some effort, too.


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Video: Postgame Interview With Jake Youso
WORCESTER, Mass. – Four different Crusaders found the back of the net including sophomore Jake Youso (International Falls, Minn.) who scored the game-winning goal to bring the Holy Cross men's hockey team a 4-1 win over Penn State at the Hart Center on Saturday afternoon in non-conference action. With the win, the Crusaders improve to 9-4-2 overall, while the Nittany Lions fall to 6-7-0 overall. The Crusaders swept the two-game series as Holy Cross defeated Penn State 5-4 in overtime on Friday. The Crusaders' current record is their best since 2005-2006 when they were 10-4-1 after the first 15 games.
Holy Cross took an early lead six minutes into the first period when senior captain Erik Vos (Carlisle, Ontario) scored a goal assisted by senior Evan Zych (Kilbride, Ontario). Vos backhanded the puck from center ice to sneak the shot past goalie PJ Musico. Holy Cross outshot Penn State 18-7. The Crusaders went 0-4 on the power play, including failing to score on two two-man advantage power plays.
The Crusaders wasted no time in the second period when Youso fired a shot into the net off of a rebound by junior Shayne Stockton (Rochester, N.Y.) to bring the Crusaders up 2-0 at just 25 seconds into the period. Freshman Joe McNamara (Chestnut Hill, Mass.) also posted an assist on the power play goal. Penn State outshot Holy Cross 11-6. The Crusaders went 1-4 on power plays while the Nittany Lions were 0-1.
Entering the third period the Crusaders advanced their lead to 3-0 when senior assistant captain Rob Linsmayer (Winnetka, Ill.) took advantage of the power play and netted the puck with help from seniors Kyle Fletcher (Kanata, Ontario) and Zych. The assist was Zych's second assist of the game and team-best 12th of the season. With 4:48 to go, Penn State found its way onto the scoreboard with a goal from junior Nate Jensen. Penn State pulled its goalie with 1:46 remaining in the third period. With 29 seconds left in the period junior Adam Schmidt (Warrington, Pa.) found the back of the empty net to make the final score 4-1. The goal was Schmidt's team-leading eighth of the season. Freshman Castan Sommer (Shrewsbury, Mass.) and sophomore Nilan Nagy (Canonsburg, Pa.) tallied assists.
The Nittany Lions outshot the Crusaders, 33-32. Holy Cross went 2-10 on the power play while Penn State went 0-4. Junior goalie Derek Kump (Falmouth, Maine) had 32 total saves and Musico had 28. With the win Kump improves to 1-1-0 for the season.
The Crusaders have now netted 11 power play goals at home this season. For every home power play goal scored the Crusaders raise money for Pink Revolution through Power Play Points for Pink. For more information and to donate go here: http://www.powerplaypointsforpink.com/. The Crusaders' annual Pink the Rink game will be on February 16 versus UConn at 7:00 p.m.
The Crusaders return to action on Sunday, Dec. 30, when they take on Yale at the New England Sports Center in Marlborough, Mass., at 2:00 p.m.


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"Of the patients who are diagnosed, very few are in the earliest stages. We have to work towards improved methods of early detection," says Dr. Spitz. "Developing more predictive risk models is a good place to start." – Margaret Spitz
Few people in the world know lung cancer statistics as well as Dr. Margaret Spitz. From age-dependent incidence rates to the effects of environmental and genetic factors, Dr. Spitz is an expert in the field. She knows that once patients are diagnosed with lung cancer, it is often too late. "In fact, while lung cancer makes up only 15% of cancer diagnoses, it is the leading cause of cancer deaths," she says.
While those statistics are terrifying for patients, they are also huge motivators for Dr. Spitz, who was founding chair of the Department of Epidemiology at the MD Anderson Cancer Center in Houston, before joining Baylor College of Medicine in 2009 to provide strategic direction in growing their population sciences program. Now she is also providing strategic direction to LUNGevity, as a member of its Scientific Advisory Board. Dr. Spitz is wielding her exceptional mastery of lung cancer epidemiology to develop ways to identify genetic and non-genetic risk factors so that earlier diagnosis is possible, when the cancer is the most treatable.
"Of the patients who are diagnosed, very few are in the earliest stages. We have to work towards improved methods of early detection," says Dr. Spitz. "Developing more predictive risk models is a good place to start."
Her approach sounds simple: create a risk factor model that identifies patients at highest risk for lung cancer and then monitor them closely. Yet developing an effective model that accounts for the vast array of risk factors, such as smoking history, family history of lung cancer and prior respiratory disease, is a monumental task requiring decades of experimentation and testing.
Nevertheless, Dr. Spitz, a world-renowned researcher with over 350 peer-reviewed publications to her name, has developed one such tool. Now scientists around the globe are studying her model in order to validate it as a risk prediction tool for lung cancer.
But Dr. Spitz is careful to note that we cannot win the fight against lung cancer in the laboratory alone. Non-profit organizations, like LUNGevity, are critical to debunking the myths surrounding lung cancer and raising public awareness. "We have allowed people, even the cancer community, to blame the victims of lung cancer," she notes. "Compared to breast and other cancers, patients with lung cancer have often been denied support and social programs that are available to other cancer patients."
But that is changing. Because even in the area of patient advocacy, Dr. Spitz says, "The key lies in the numbers. And now we have great numbers. This is a great time to be involved with LUNGevity; there is now even more momentum to make real changes through lung cancer research."
Please find more information on Dr. Spitz here.